@article{
 title = {Enhancing luciferase activity and stability through generative modeling of natural enzyme sequences},
 type = {article},
 year = {2023},
 keywords = {enzyme catalysis,enzyme design,generative model,mutation effects,natural evolution},
 pages = {e2312848120},
 volume = {120},
 websites = {https://www.pnas.org/doi/abs/10.1073/pnas.2312848120},
 month = {11},
 publisher = {National Academy of Sciences},
 day = {20},
 id = {d266d66a-f97d-3982-b664-7b17442a89a0},
 created = {2023-11-27T18:30:52.876Z},
 accessed = {2023-11-27},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2024-06-06T20:00:43.063Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 citation_key = {Xie2023},
 private_publication = {false},
 abstract = {SignificanceGenerative models, when trained on natural protein sequences, have the capacity to generate novel sequences displaying enzyme activity. However, strategically inducing mutations to boos...},
 bibtype = {article},
 author = {Xie, Wen Jun and Liu, Dangliang and Wang, Xiaoya and Zhang, Aoxuan and Wei, Qijia and Nandi, Ashim and Dong, Suwei and Warshel, Arieh},
 doi = {10.1073/PNAS.2312848120},
 journal = {Proc Natl Acad Sci U S A},
 number = {48}
}

SignificanceGenerative models, when trained on natural protein sequences, have the capacity to generate novel sequences displaying enzyme activity. However, strategically inducing mutations to boos...

@article{
 title = {Enhancing computational enzyme design by a maximum entropy strategy},
 type = {article},
 year = {2022},
 pages = {e2122355119},
 volume = {119},
 id = {d6ba9704-3123-3ca0-8eee-ac54b7e94417},
 created = {2022-01-10T06:34:22.479Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2024-04-08T16:55:52.670Z},
 read = {true},
 starred = {true},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Xie2022a},
 folder_uuids = {650d6180-635a-442e-888b-acc52e330fc1},
 private_publication = {false},
 bibtype = {article},
 author = {Xie, Wen Jun and Asadi, Mojgan and Warshel, Arieh},
 journal = {Proc Natl Acad Sci U S A},
 number = {7}
}

@article{
 title = {Electrostatic influence on IL-1 transport through the GSDMD pore},
 type = {article},
 year = {2022},
 pages = {e2120287119},
 volume = {119},
 id = {d80dce3f-72f0-3538-914a-615aa98628bf},
 created = {2022-02-09T03:56:57.918Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2023-08-14T21:28:53.943Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 citation_key = {Xie2022},
 private_publication = {false},
 bibtype = {article},
 author = {Xie, Wen Jun and Xia, Shiyu and Warshel, Arieh and Wu, Hao},
 doi = {10.1073/pnas.2120287119/-/DCSupplemental.Published},
 journal = {Proceedings of the National Academy of Sciences of the United States of America}
}

@article{
 title = {pH regulates potassium conductance and drives a constitutive proton current in human TMEM175},
 type = {article},
 year = {2022},
 pages = {eabm1568},
 volume = {8},
 websites = {https://www.science.org/doi/full/10.1126/sciadv.abm1568},
 month = {3},
 publisher = {American Association for the Advancement of Science},
 day = {25},
 id = {c92f4e90-4694-34fd-96d1-3a41234f6fdd},
 created = {2022-04-09T02:51:09.411Z},
 accessed = {2022-04-08},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2023-08-14T21:28:53.555Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 citation_key = {Zheng2022},
 private_publication = {false},
 abstract = {Human TMEM175, a noncanonical potassium (K+) channel in endolysosomes, contributes to their pH stability and is implicated in the pathogenesis of Parkinson’s disease (PD). Structurally, the TMEM175...},
 bibtype = {article},
 author = {Zheng, Wang and Shen, Chen and Wang, Longfei and Rawson, Shaun and Xie, Wen Jun and Nist-Lund, Carl and Wu, Jason and Shen, Zhangfei and Xia, Shiyu and Holt, Jeffrey R. and Wu, Hao and Fu, Tian-Min},
 doi = {10.1126/SCIADV.ABM1568},
 journal = {Science Advances},
 number = {12}
}

Human TMEM175, a noncanonical potassium (K+) channel in endolysosomes, contributes to their pH stability and is implicated in the pathogenesis of Parkinson’s disease (PD). Structurally, the TMEM175...

@article{
 title = {Natural evolution provides strong hints about laboratory evolution of designer enzymes},
 type = {article},
 year = {2022},
 pages = {e2207904119},
 volume = {119},
 id = {d8a550df-00c0-398e-bb9b-952cf95edcc1},
 created = {2022-07-28T23:40:16.996Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2024-01-10T22:19:13.428Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Xie2022b},
 private_publication = {false},
 bibtype = {article},
 author = {Xie, Wen Jun and Warshel, Arieh},
 doi = {10.1073/pnas.2207904119/-/DCSupplemental.Published},
 journal = {Proc Natl Acad Sci U S A},
 number = {31}
}

@article{
 title = {Exploring the role of chemical reactions in the selectivity of tyrosine kinase inhibitors},
 type = {article},
 year = {2022},
 pages = {16638−16646},
 volume = {144},
 id = {626edaef-0001-317c-ae2b-cff76dfde35e},
 created = {2022-08-31T06:20:22.218Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2023-08-14T21:28:53.758Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Asadi2022},
 private_publication = {false},
 bibtype = {article},
 author = {Asadi, Mojgan and Xie, Wen Jun and Warshel, Arieh},
 journal = {Journal of the American Chemical Society}
}

@misc{
 title = {System and method for computational enzyme design based on maximum entropy},
 type = {misc},
 year = {2021},
 pages = {US application no. 63/234,099},
 revision = {US patent application},
 id = {c72d5141-9713-31a1-b22e-b4a3ea407eae},
 created = {2022-03-08T08:25:00.825Z},
 file_attached = {false},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2023-08-14T21:28:53.935Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Warshel2021},
 private_publication = {false},
 bibtype = {misc},
 author = {Warshel, Arieh and Xie, Wen Jun}
}

@article{
 title = {Characterizing chromatin folding coordinate and landscape with deep learning},
 type = {article},
 year = {2020},
 pages = {e1008262},
 volume = {16},
 id = {5896598c-6f9a-359e-9709-204f47a72036},
 created = {2020-03-03T01:16:37.327Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2020-10-18T00:21:45.998Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Xie2019},
 private_publication = {false},
 abstract = {Genome organization is critical for setting up the spatial environment of gene transcription, and substantial progress has been made towards its high-resolution characterization. The underlying molecular mechanism for its establishment is much less understood. We applied a deep-learning approach, variational autoencoder (VAE), to analyze the fluctuation and heterogeneity of chromatin structures revealed by single-cell super-resolution imaging and to identify a reaction coordinate for chromatin folding. This coordinate monitors the progression of topologically associating domain (TAD) formation and connects the seemingly random structures observed in individual cohesin-depleted cells as intermediate states along the folding pathway. Analysis of the folding landscape derived from VAE suggests that well-folded structures similar to those found in wild-type cells remain energetically favorable in cohesin-depleted cells. The interaction energies, however, are not strong enough to overcome the entropic penalty, leading to the formation of only partially folded structures and the disappearance of TADs from contact maps upon averaging. Implications of these results for the molecular driving forces of chromatin folding are discussed.},
 bibtype = {article},
 author = {Xie, Wen Jun and Qi, Yifeng and Zhang, Bin},
 doi = {10.1101/824417},
 journal = {PLoS Comput Biol},
 number = {9}
}

Genome organization is critical for setting up the spatial environment of gene transcription, and substantial progress has been made towards its high-resolution characterization. The underlying molecular mechanism for its establishment is much less understood. We applied a deep-learning approach, variational autoencoder (VAE), to analyze the fluctuation and heterogeneity of chromatin structures revealed by single-cell super-resolution imaging and to identify a reaction coordinate for chromatin folding. This coordinate monitors the progression of topologically associating domain (TAD) formation and connects the seemingly random structures observed in individual cohesin-depleted cells as intermediate states along the folding pathway. Analysis of the folding landscape derived from VAE suggests that well-folded structures similar to those found in wild-type cells remain energetically favorable in cohesin-depleted cells. The interaction energies, however, are not strong enough to overcome the entropic penalty, leading to the formation of only partially folded structures and the disappearance of TADs from contact maps upon averaging. Implications of these results for the molecular driving forces of chromatin folding are discussed.

@article{
 title = {Single-molecule and in silico dissection of the interaction between Polycomb repressive complex 2 and chromatin},
 type = {article},
 year = {2020},
 keywords = {Epigenetics,Heterochromatin,Molecular dynamics simulation,Polycomb-group protein,Single-molecule force spectroscopy},
 pages = {30465-30475},
 volume = {117},
 id = {a6deb9b3-4efe-3f71-ba5f-3462af4c8289},
 created = {2022-03-27T01:06:05.423Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2023-08-14T21:28:53.933Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Leicher2020},
 private_publication = {false},
 abstract = {Polycomb repressive complex 2 (PRC2) installs and spreads repressive histone methylation marks on eukaryotic chromosomes. Because of the key roles that PRC2 plays in development and disease, how this epigenetic machinery interacts with DNA and nucleosomes is of major interest. Nonetheless, the mechanism by which PRC2 engages with native-like chromatin remains incompletely understood. In this work, we employ single-molecule force spectroscopy and molecular dynamics simulations to dissect the behavior of PRC2 on polynucleosome arrays. Our results reveal an unexpectedly diverse repertoire of PRC2 binding configurations on chromatin. Besides reproducing known binding modes in which PRC2 interacts with bare DNA, mononucleosomes, and adjacent nucleosome pairs, our data also provide direct evidence that PRC2 can bridge pairs of distal nucleosomes. In particular, the “1–3” bridging mode, in which PRC2 engages two nucleosomes separated by one spacer nucleosome, is a preferred low-energy configuration. Moreover, we show that the distribution and stability of different PRC2–chromatin interaction modes are modulated by accessory subunits, oncogenic histone mutations, and the methylation state of chromatin. Overall, these findings have implications for the mechanism by which PRC2 spreads histone modifications and compacts chromatin. The experimental and computational platforms developed here provide a framework for understanding the molecular basis of epigenetic maintenance mediated by Polycomb-group proteins.},
 bibtype = {article},
 author = {Leicher, Rachel and Ge, Eva J. and Lin, Xingcheng and Reynolds, Matthew J. and Xie, Wenjun and Walz, Thomas and Zhang, Bin and Muir, Tom W. and Liu, Shixin},
 doi = {10.1073/pnas.2003395117},
 journal = {Proceedings of the National Academy of Sciences of the United States of America},
 number = {48}
}

Polycomb repressive complex 2 (PRC2) installs and spreads repressive histone methylation marks on eukaryotic chromosomes. Because of the key roles that PRC2 plays in development and disease, how this epigenetic machinery interacts with DNA and nucleosomes is of major interest. Nonetheless, the mechanism by which PRC2 engages with native-like chromatin remains incompletely understood. In this work, we employ single-molecule force spectroscopy and molecular dynamics simulations to dissect the behavior of PRC2 on polynucleosome arrays. Our results reveal an unexpectedly diverse repertoire of PRC2 binding configurations on chromatin. Besides reproducing known binding modes in which PRC2 interacts with bare DNA, mononucleosomes, and adjacent nucleosome pairs, our data also provide direct evidence that PRC2 can bridge pairs of distal nucleosomes. In particular, the “1–3” bridging mode, in which PRC2 engages two nucleosomes separated by one spacer nucleosome, is a preferred low-energy configuration. Moreover, we show that the distribution and stability of different PRC2–chromatin interaction modes are modulated by accessory subunits, oncogenic histone mutations, and the methylation state of chromatin. Overall, these findings have implications for the mechanism by which PRC2 spreads histone modifications and compacts chromatin. The experimental and computational platforms developed here provide a framework for understanding the molecular basis of epigenetic maintenance mediated by Polycomb-group proteins.

@article{
 title = {Molecular mechanism for NLRP6 inflammasome assembly and activation},
 type = {article},
 year = {2019},
 pages = {2052-2057},
 volume = {116},
 id = {fd532032-9116-35f9-b895-beec6f6eabca},
 created = {2019-03-17T18:03:19.184Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2020-08-12T04:26:59.367Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Shen2019},
 private_publication = {false},
 abstract = {Inflammasomes are large protein complexes that trigger host defense in cells by activating inflammatory caspases for cytokine maturation and pyroptosis. NLRP6 is a sensor protein in the nucleotide-binding domain (NBD) and leucine-rich repeat (LRR)-containing (NLR) inflammasome family that has been shown to play multiple roles in regulating inflammation and host defenses. Despite the significance of the NLRP6 inflammasome, little is known about the molecular mechanism behind its assembly and activation. Here we present cryo-EM and crystal structures of NLRP6 pyrin domain (PYD). We show that NLRP6 PYD alone is able to self-assemble into filamentous structures accompanied by large conformational changes and can recruit the ASC adaptor using PYD–PYD interactions. Using molecular dynamics simulations, we identify the surface that the NLRP6 PYD filament uses to recruit ASC PYD. We further find that full-length NLRP6 assembles in a concentration-dependent manner into wider filaments with a PYD core surrounded by the NBD and the LRR domain. These findings provide a structural understanding of inflammasome assembly by NLRP6 and other members of the NLR family.},
 bibtype = {article},
 author = {Shen, Chen and Lu, Alvin and Xie, Wen Jun and Ruan, Jianbin and Negro, Roberto and Egelman, Edward H. and Fu, Tian Min and Wu, Hao},
 doi = {10.1073/pnas.1817221116},
 journal = {Proceedings of the National Academy of Sciences of the United States of America}
}

Inflammasomes are large protein complexes that trigger host defense in cells by activating inflammatory caspases for cytokine maturation and pyroptosis. NLRP6 is a sensor protein in the nucleotide-binding domain (NBD) and leucine-rich repeat (LRR)-containing (NLR) inflammasome family that has been shown to play multiple roles in regulating inflammation and host defenses. Despite the significance of the NLRP6 inflammasome, little is known about the molecular mechanism behind its assembly and activation. Here we present cryo-EM and crystal structures of NLRP6 pyrin domain (PYD). We show that NLRP6 PYD alone is able to self-assemble into filamentous structures accompanied by large conformational changes and can recruit the ASC adaptor using PYD–PYD interactions. Using molecular dynamics simulations, we identify the surface that the NLRP6 PYD filament uses to recruit ASC PYD. We further find that full-length NLRP6 assembles in a concentration-dependent manner into wider filaments with a PYD core surrounded by the NBD and the LRR domain. These findings provide a structural understanding of inflammasome assembly by NLRP6 and other members of the NLR family.

@article{
 title = {Interlayer hopping dynamics of bilayer water confined between graphene sheets},
 type = {article},
 year = {2019},
 keywords = {Activated hopping dynamics,Confined water,Large angular jump mechanism,Molecular dynamics simulation,Transition path ensemble analysis},
 pages = {153-159},
 volume = {722},
 websites = {https://doi.org/10.1016/j.cplett.2019.02.046},
 publisher = {Elsevier},
 id = {eb196705-deb1-33fd-843b-17b5017afebc},
 created = {2019-03-24T04:40:23.306Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2020-08-12T04:26:58.747Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Qiao2019},
 private_publication = {false},
 abstract = {The ubiquitous existence of water confined in nano-capillaries is key to fundamental biological and technological applications. Using molecular dynamics simulations, we analyzed the hopping-like interlayer relocation dynamics of bilayer water confined between two parallel graphene sheets. In contrary to the common scheme that relocation is driven by density fluctuations, analysis of the transition path ensemble revealed that interlayer hopping is induced by local hydrogen bond configuration fluctuations coupled with activated consecutive transient angular reorientations. Our results consolidated the anisotropic nature of water relocation under strong ordering, which provided a mechanistic insight into the relaxation behavior at glass-forming water's fragile-to-strong crossover.},
 bibtype = {article},
 author = {Qiao, Zhuoran and Xie, Wen Jun and Cai, Xiaoxia and Gao, Yi Qin},
 doi = {10.1016/j.cplett.2019.02.046},
 journal = {Chemical Physics Letters}
}

The ubiquitous existence of water confined in nano-capillaries is key to fundamental biological and technological applications. Using molecular dynamics simulations, we analyzed the hopping-like interlayer relocation dynamics of bilayer water confined between two parallel graphene sheets. In contrary to the common scheme that relocation is driven by density fluctuations, analysis of the transition path ensemble revealed that interlayer hopping is induced by local hydrogen bond configuration fluctuations coupled with activated consecutive transient angular reorientations. Our results consolidated the anisotropic nature of water relocation under strong ordering, which provided a mechanistic insight into the relaxation behavior at glass-forming water's fragile-to-strong crossover.

@article{
 title = {Learning the formation mechanism of domain-level chromatin states with epigenomics data},
 type = {article},
 year = {2019},
 pages = {2047-2056},
 volume = {116},
 websites = {https://doi.org/10.1016/j.bpj.2019.04.006},
 publisher = {Biophysical Society},
 id = {b4698dcc-97ec-3f5c-b185-bdb4da6eae0a},
 created = {2019-11-07T19:04:06.446Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2021-03-30T07:37:01.214Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Xie2019},
 folder_uuids = {5a581cdf-c2f7-40cd-b429-bb4991430339},
 private_publication = {false},
 abstract = {Epigenetic modifications can extend over long genomic regions to form domain-level chromatin states that play critical roles in gene regulation. The molecular mechanism for the establishment and maintenance of these states is not fully understood and remains challenging to study with existing experimental techniques. Here, we took a data-driven approach and parameterized an information-theoretic model to infer the formation mechanism of domain-level chromatin states from genome-wide epigenetic modification profiles. This model reproduces statistical correlations among histone modifications and identifies well-known states. Importantly, it predicts drastically different mechanisms and kinetic pathways for the formation of euchromatin and heterochromatin. In particular, long, strong enhancer and promoter states grow gradually from short but stable regulatory elements via a multistep process. On the other hand, the formation of heterochromatin states is highly cooperative, and no intermediate states are found along the transition path. This cooperativity can arise from a chromatin looping-mediated spreading of histone methylation mark and supports collapsed, globular three-dimensional conformations rather than regular fibril structures for heterochromatin. We further validated these predictions using changes of epigenetic profiles along cell differentiation. Our study demonstrates that information-theoretic models can go beyond statistical analysis to derive insightful kinetic information that is otherwise difficult to access.},
 bibtype = {article},
 author = {Xie, Wen Jun and Zhang, Bin},
 doi = {10.1016/j.bpj.2019.04.006},
 journal = {Biophysical Journal}
}

Epigenetic modifications can extend over long genomic regions to form domain-level chromatin states that play critical roles in gene regulation. The molecular mechanism for the establishment and maintenance of these states is not fully understood and remains challenging to study with existing experimental techniques. Here, we took a data-driven approach and parameterized an information-theoretic model to infer the formation mechanism of domain-level chromatin states from genome-wide epigenetic modification profiles. This model reproduces statistical correlations among histone modifications and identifies well-known states. Importantly, it predicts drastically different mechanisms and kinetic pathways for the formation of euchromatin and heterochromatin. In particular, long, strong enhancer and promoter states grow gradually from short but stable regulatory elements via a multistep process. On the other hand, the formation of heterochromatin states is highly cooperative, and no intermediate states are found along the transition path. This cooperativity can arise from a chromatin looping-mediated spreading of histone methylation mark and supports collapsed, globular three-dimensional conformations rather than regular fibril structures for heterochromatin. We further validated these predictions using changes of epigenetic profiles along cell differentiation. Our study demonstrates that information-theoretic models can go beyond statistical analysis to derive insightful kinetic information that is otherwise difficult to access.

@article{
 title = {Combined immunodeficiency caused by a loss-of-function mutation in DNA polymerase delta 1},
 type = {article},
 year = {2019},
 keywords = {DNA polymerase delta 1,DNA polymerase δ1 catalytic subunit,POLD1,primary immunodeficiency,replication factor C,whole-exome sequencing},
 pages = {391-401.e8},
 volume = {145},
 id = {b88103b0-5895-3880-b991-5290f52a7b41},
 created = {2020-03-03T01:16:37.500Z},
 file_attached = {false},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2020-08-12T04:26:58.915Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Cui2019},
 private_publication = {false},
 abstract = {Background: Mutations affecting DNA polymerases have been implicated in genomic instability and cancer development, but the mechanisms by which they can affect the immune system remain largely unexplored. Objective: We sought to establish the role of DNA polymerase δ1 catalytic subunit (POLD1) as the cause of a primary immunodeficiency in an extended kindred. Methods: We performed whole-exome and targeted gene sequencing, lymphocyte characterization, molecular and functional analyses of the DNA polymerase δ (Polδ) complex, and T- and B-cell antigen receptor repertoire analysis. Results: We identified a missense mutation (c. 3178C>T; p.R1060C) in POLD1 in 3 related subjects who presented with recurrent, especially herpetic, infections and T-cell lymphopenia with impaired T-cell but not B-cell proliferation. The mutation destabilizes the Polδ complex, leading to ineffective recruitment of replication factor C to initiate DNA replication. Molecular dynamics simulation revealed that the R1060C mutation disrupts the intramolecular interaction between the POLD1 CysB motif and the catalytic domain and also between POLD1 and the Polδ subunit POLD2. The patients exhibited decreased numbers of naive CD4 and especially CD8 T cells in favor of effector memory subpopulations. This skewing was associated with oligoclonality and restricted T-cell receptor β-chain V-J pairing in CD8+ but not CD4+ T cells, suggesting that POLD1R1060C differentially affects peripheral CD8+ T-cell expansion and possibly thymic selection. Conclusion: These results identify gene defects in POLD1 as a novel cause of T-cell immunodeficiency.},
 bibtype = {article},
 author = {Cui, Ye and Keles, Sevgi and Charbonnier, Louis Marie and Julé, Amélie M. and Henderson, Lauren and Celik, Seyma Celikbilek and Reisli, Ismail and Shen, Chen and Xie, Wen Jun and Schmitz-Abe, Klaus and Wu, Hao and Chatila, Talal A.},
 doi = {10.1016/j.jaci.2019.10.004},
 journal = {Journal of Allergy and Clinical Immunology}
}

Background: Mutations affecting DNA polymerases have been implicated in genomic instability and cancer development, but the mechanisms by which they can affect the immune system remain largely unexplored. Objective: We sought to establish the role of DNA polymerase δ1 catalytic subunit (POLD1) as the cause of a primary immunodeficiency in an extended kindred. Methods: We performed whole-exome and targeted gene sequencing, lymphocyte characterization, molecular and functional analyses of the DNA polymerase δ (Polδ) complex, and T- and B-cell antigen receptor repertoire analysis. Results: We identified a missense mutation (c. 3178C>T; p.R1060C) in POLD1 in 3 related subjects who presented with recurrent, especially herpetic, infections and T-cell lymphopenia with impaired T-cell but not B-cell proliferation. The mutation destabilizes the Polδ complex, leading to ineffective recruitment of replication factor C to initiate DNA replication. Molecular dynamics simulation revealed that the R1060C mutation disrupts the intramolecular interaction between the POLD1 CysB motif and the catalytic domain and also between POLD1 and the Polδ subunit POLD2. The patients exhibited decreased numbers of naive CD4 and especially CD8 T cells in favor of effector memory subpopulations. This skewing was associated with oligoclonality and restricted T-cell receptor β-chain V-J pairing in CD8+ but not CD4+ T cells, suggesting that POLD1R1060C differentially affects peripheral CD8+ T-cell expansion and possibly thymic selection. Conclusion: These results identify gene defects in POLD1 as a novel cause of T-cell immunodeficiency.

@article{
 title = {Structure of water confined between two parallel graphene plates},
 type = {article},
 year = {2019},
 pages = {124703},
 volume = {150},
 id = {39653735-cbb3-3cb4-bf0c-9b24ea975430},
 created = {2020-03-03T01:16:37.530Z},
 file_attached = {false},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2020-08-12T04:26:58.919Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Cai2019},
 private_publication = {false},
 abstract = {We study, in this paper, the physical properties of water confined between two parallel graphene plates with different slit widths to understand the effects of confinement on the water structure and how bulk properties are reached as the water layer thickens. It was found that the microscopic structures of the interfacial liquid layer close to graphene vary with the slit width. Water tends to locate at the center of the six-membered ring of graphene planes to form triangular patterns, as found by others. The narrower the slit width is, the more pronounced this pattern is, except for the slit width of 9.5 Å, for which a well-defined two-layer structure of water forms. On the other hand, squared structures can be clearly seen in single snapshots at small (6.5 Å and 7.5 Å) but not large slit widths. Even at small slit widths, the square-like geometry is observed only when an average is taken for a short trajectory, and averaging over a long time yields a triangular pattern dictated by the graphene geometry. We estimate the length of time needed to observe two patterns, respectively. We also used the two-phase thermodynamic model to study the variation of entropy of confined water and found that at 8.5 Å, the entropy of confined water is larger than that of bulk water. The rotational entropy of confined water is higher than that of bulk water for all slit widths due to the reduction of the hydrogen bond in the confined space.},
 bibtype = {article},
 author = {Cai, Xiaoxia and Xie, Wen Jun and Yang, Ying and Long, Zhuoran and Zhang, Jun and Qiao, Zhuoran and Yang, Lijiang and Gao, Yi Qin},
 doi = {10.1063/1.5080788},
 journal = {Journal of Chemical Physics}
}

We study, in this paper, the physical properties of water confined between two parallel graphene plates with different slit widths to understand the effects of confinement on the water structure and how bulk properties are reached as the water layer thickens. It was found that the microscopic structures of the interfacial liquid layer close to graphene vary with the slit width. Water tends to locate at the center of the six-membered ring of graphene planes to form triangular patterns, as found by others. The narrower the slit width is, the more pronounced this pattern is, except for the slit width of 9.5 Å, for which a well-defined two-layer structure of water forms. On the other hand, squared structures can be clearly seen in single snapshots at small (6.5 Å and 7.5 Å) but not large slit widths. Even at small slit widths, the square-like geometry is observed only when an average is taken for a short trajectory, and averaging over a long time yields a triangular pattern dictated by the graphene geometry. We estimate the length of time needed to observe two patterns, respectively. We also used the two-phase thermodynamic model to study the variation of entropy of confined water and found that at 8.5 Å, the entropy of confined water is larger than that of bulk water. The rotational entropy of confined water is higher than that of bulk water for all slit widths due to the reduction of the hydrogen bond in the confined space.

@article{
 title = {Large hydrogen-bond mismatch between TMAO and urea promotes their hydrophobic association},
 type = {article},
 year = {2018},
 pages = {2615-2627},
 volume = {4},
 websites = {https://linkinghub.elsevier.com/retrieve/pii/S2451929418303723},
 publisher = {Elsevier Inc.},
 id = {bfd2b7c1-2056-3408-a8c8-b96bd5664dad},
 created = {2018-09-16T15:31:49.002Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2020-05-11T21:11:29.978Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Xie2018},
 private_publication = {false},
 bibtype = {article},
 author = {Xie, Wen Jun and Cha, Seoncheol and Ohto, Tatsuhiko and Mizukami, Wataru and Mao, Yuezhi and Wagner, Manfred and Bonn, Mischa and Hunger, Johannes and Nagata, Yuki},
 doi = {10.1016/j.chempr.2018.08.020},
 journal = {Chem}
}

@article{
 title = {The effect of hydration number on the interfacial transport of sodium ions},
 type = {article},
 year = {2018},
 pages = {701-705},
 volume = {557},
 id = {3ebecd9c-06e5-3bba-a2f8-d606c9803251},
 created = {2019-03-24T04:40:23.319Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2020-08-12T04:26:58.762Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Peng2018},
 private_publication = {false},
 bibtype = {article},
 author = {Peng, Jinbo and Cao, Duanyun and He, Zhili and Guo, Jing and Hapala, Prokop and Ma, Runze and Cheng, Bowei and Chen, Ji and Xie, Wen Jun and Li, Xin Zheng and Jelínek, Pavel and Xu, Li Mei and Gao, Yi Qin and Wang, En Ge and Jiang, Ying},
 doi = {10.1038/s41586-018-0473-8},
 journal = {Nature}
}

@article{
 title = {Definition of free O-H groups of water at the air-water interface},
 type = {article},
 year = {2018},
 pages = {357-364},
 volume = {14},
 id = {02ff1db2-3074-3f4f-a643-7bab69c04b1d},
 created = {2020-03-03T01:16:37.327Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2022-08-13T04:57:39.875Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Tang2018},
 private_publication = {false},
 abstract = {Free O-H groups of water are often found at the water-hydrophobic medium interface, e.g. for water contact with hydrophobic protein residues, or at the water-air interface. In surface-specific vibrational spectroscopic studies using sum-frequency generation (SFG) spectroscopy, free O-H groups are experimentally well characterized in the O-H stretch region by a sharp 3700 cm-1 peak. Although these free O-H groups are often defined as the O-H groups which are not hydrogen-bonded to other water molecules, a direct correlation between such non-hydrogen-bonded O-H groups and the 3700 cm-1 SFG response has been lacking. Our data show that commonly used hydrogen bond definitions do not adequately capture the free O-H groups contributing to the 3700 cm-1 peak. We thus formulate a new definition for capturing the subensemble of the surface free O-H groups using the intermolecular distance and the angle formed by the water dimer, through the comparison of the ∼3700 cm-1 SFG response and the responses from the selected free O-H groups at the HOD-air interface. Using these optimized free O-H group definitions, we infer the fraction of interfacial water molecules with free O-H groups of 28%, a vibrational lifetime of the free O-H groups of 1.3 ps, and the angle formed by the free O-H groups and the surface normal of 67° at the water-air interface. We expect that this improved free O-H group definition can be helpful in exploring the structure and dynamics of the interfacial water.},
 bibtype = {article},
 author = {Tang, Fujie and Ohto, Tatsuhiko and Hasegawa, Taisuke and Xie, Wen Jun and Xu, Limei and Bonn, Mischa and Nagata, Yuki},
 doi = {10.1021/acs.jctc.7b00566},
 journal = {Journal of Chemical Theory and Computation}
}

Free O-H groups of water are often found at the water-hydrophobic medium interface, e.g. for water contact with hydrophobic protein residues, or at the water-air interface. In surface-specific vibrational spectroscopic studies using sum-frequency generation (SFG) spectroscopy, free O-H groups are experimentally well characterized in the O-H stretch region by a sharp 3700 cm-1 peak. Although these free O-H groups are often defined as the O-H groups which are not hydrogen-bonded to other water molecules, a direct correlation between such non-hydrogen-bonded O-H groups and the 3700 cm-1 SFG response has been lacking. Our data show that commonly used hydrogen bond definitions do not adequately capture the free O-H groups contributing to the 3700 cm-1 peak. We thus formulate a new definition for capturing the subensemble of the surface free O-H groups using the intermolecular distance and the angle formed by the water dimer, through the comparison of the ∼3700 cm-1 SFG response and the responses from the selected free O-H groups at the HOD-air interface. Using these optimized free O-H group definitions, we infer the fraction of interfacial water molecules with free O-H groups of 28%, a vibrational lifetime of the free O-H groups of 1.3 ps, and the angle formed by the free O-H groups and the surface normal of 67° at the water-air interface. We expect that this improved free O-H group definition can be helpful in exploring the structure and dynamics of the interfacial water.

@article{
 title = {Simulation studies of the self-assembly of halogen-bonded sierpiński triangle fractals},
 type = {article},
 year = {2017},
 keywords = {Catassembly,Fractal,Monte carlo simulation,Self-assembly,Sierpiński triangle},
 pages = {539-547},
 volume = {33},
 id = {55bfb220-298f-3fe1-bac8-aaf16a486014},
 created = {2020-03-03T01:16:37.325Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2022-06-06T18:14:41.179Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Zhang2017a},
 private_publication = {false},
 abstract = {In this study, a coarse-grained lattice Monte Carlo model was used to investigate the formation of Sierpiński triangle (ST) fractals through self-assembly on a triangular lattice surface. In the simulations, both symmetric and asymmetric molecular building blocks can spontaneously form ST fractal patterns, although the mixture of enantiomers of asymmetric molecule is more difficult to self-organize into ST of a high order owing to the presence of a large variety of competing three-membered nodes. The formation of ST fractals is favored at low surface coverage and is sensitive to temperature. Furthermore, to test whether the assembly pathway and outcome could be controlled by molecular design, we guided the self-assembly process forming ST fractal into the otherwise disfavored self-assembled structures using templates different from the assembling molecules. The templates are designed to act as “catassemblers” that initiate the self-assembling but are excluded from the final assembled structure.},
 bibtype = {article},
 author = {Zhang, Zhen and Xie, Wen Jun and Yang, Yi Isaac and Sun, Geng and Gao, Yi Qin},
 doi = {10.3866/PKU.WHXB201611252},
 journal = {Acta Physico - Chimica Sinica}
}

In this study, a coarse-grained lattice Monte Carlo model was used to investigate the formation of Sierpiński triangle (ST) fractals through self-assembly on a triangular lattice surface. In the simulations, both symmetric and asymmetric molecular building blocks can spontaneously form ST fractal patterns, although the mixture of enantiomers of asymmetric molecule is more difficult to self-organize into ST of a high order owing to the presence of a large variety of competing three-membered nodes. The formation of ST fractals is favored at low surface coverage and is sensitive to temperature. Furthermore, to test whether the assembly pathway and outcome could be controlled by molecular design, we guided the self-assembly process forming ST fractal into the otherwise disfavored self-assembled structures using templates different from the assembling molecules. The templates are designed to act as “catassemblers” that initiate the self-assembling but are excluded from the final assembled structure.

@article{
 title = {Single mutations reshape the structural correlation network of the DMXAA-human STING complex},
 type = {article},
 year = {2017},
 pages = {2073-2082},
 volume = {121},
 id = {5fb0b525-16af-3f24-b1cd-47e3a276b596},
 created = {2020-03-03T01:16:37.337Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2022-12-09T01:57:43.583Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Che2017},
 private_publication = {false},
 abstract = {Subtle changes in protein sequences are able to alter ligand-protein interactions. Unraveling the mechanism of such phenomena is important for understanding ligand-protein interactions, including the DMXAA-STING interaction. DMXAA specifically binds to mouse STING instead of human STING. However, the S162A mutation and a newly discovered E260I mutation endow human STINGAQ with DMXAA sensitivity. Through molecular dynamics simulations, we revealed how these single mutations alter the DMXAA-STING interaction. Compared to mutated systems, structural correlations in the interaction of STINGAQ with DMXAA are stronger, and the correlations are cross-protomers in the dimeric protein. Analyses on correlation coefficients lead to the identification of two key interactions that mediate the strong cross-protomer correlation in the DMXAA-STINGAQ interaction network: DMXAA-267T-162S∗ and 238R-260E∗. These two interactions are partially and totally interrupted by the S162A and E260I mutations, respectively. Moreover, a smaller number of water molecules are displaced upon DMXAA binding to STINGAQ than that on binding to its mutants, leading to a larger entropic penalty for the former. Considering the sensitivity of STINGAQ and two of its mutants to DMXAA, a strong structural correlation appears to discourage DMXAA-STING binding. Such an observation suggests that DMXAA derivatives, which are deprived of hydrogen-bond interaction with both 162S∗ and 267T, are potential agonists of human STING. (Figure Presented).},
 bibtype = {article},
 author = {Che, Xing and Du, Xiao Xia and Cai, Xiaoxia and Zhang, Jun and Xie, Wen Jun and Long, Zhuoran and Ye, Zhao Yang and Zhang, Heng and Yang, Lijiang and Su, Xiao Dong and Gao, Yi Qin},
 doi = {10.1021/acs.jpcb.6b12472},
 journal = {Journal of Physical Chemistry B}
}

Subtle changes in protein sequences are able to alter ligand-protein interactions. Unraveling the mechanism of such phenomena is important for understanding ligand-protein interactions, including the DMXAA-STING interaction. DMXAA specifically binds to mouse STING instead of human STING. However, the S162A mutation and a newly discovered E260I mutation endow human STINGAQ with DMXAA sensitivity. Through molecular dynamics simulations, we revealed how these single mutations alter the DMXAA-STING interaction. Compared to mutated systems, structural correlations in the interaction of STINGAQ with DMXAA are stronger, and the correlations are cross-protomers in the dimeric protein. Analyses on correlation coefficients lead to the identification of two key interactions that mediate the strong cross-protomer correlation in the DMXAA-STINGAQ interaction network: DMXAA-267T-162S∗ and 238R-260E∗. These two interactions are partially and totally interrupted by the S162A and E260I mutations, respectively. Moreover, a smaller number of water molecules are displaced upon DMXAA binding to STINGAQ than that on binding to its mutants, leading to a larger entropic penalty for the former. Considering the sensitivity of STINGAQ and two of its mutants to DMXAA, a strong structural correlation appears to discourage DMXAA-STING binding. Such an observation suggests that DMXAA derivatives, which are deprived of hydrogen-bond interaction with both 162S∗ and 267T, are potential agonists of human STING. (Figure Presented).

@article{
 title = {DNA methylation landscape reflects the spatial organization of chromatin in different cells},
 type = {article},
 year = {2017},
 pages = {1395-1404},
 volume = {113},
 websites = {https://doi.org/10.1016/j.bpj.2017.08.019},
 publisher = {Biophysical Society},
 id = {525f4704-c445-359b-9833-039179b10bf0},
 created = {2022-03-08T08:24:59.286Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2023-08-14T21:28:53.929Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Zhang2017},
 private_publication = {false},
 abstract = {The relationship between DNA methylation and chromatin structure is still largely unknown. By analyzing a large set of published sequencing data, we observed a long-range power law correlation of DNA methylation with cell class-specific scaling exponents in the range of tens of kilobases. We showed that such cell class-specific scaling exponents are caused by different patchiness of DNA methylation in different cells. By modeling the chromatin structure using high-resolution chromosome conformation capture data and mapping the methylation level onto the modeled structure, we demonstrated that the patchiness of DNA methylation is related to chromatin structure. The scaling exponents of the power law correlation are thus a display of the spatial organization of chromatin. Besides the long-range correlation, we also showed that the local correlation of DNA methylation is associated with nucleosome positioning. The local correlation of partially methylated domains is different from that of nonpartially methylated domains, suggesting that their chromatin structures differ at the scale of several hundred base pairs (covering a few nucleosomes). Our study provides a novel, to our knowledge, view of the spatial organization of chromatin structure from a perspective of DNA methylation, in which both long-range and local correlations of DNA methylation along the genome reflect the spatial organization of chromatin.},
 bibtype = {article},
 author = {Zhang, Ling and Xie, Wen Jun and Liu, Sirui and Meng, Luming and Gu, Chan and Gao, Yi Qin},
 doi = {10.1016/j.bpj.2017.08.019},
 journal = {Biophysical Journal},
 number = {7}
}

The relationship between DNA methylation and chromatin structure is still largely unknown. By analyzing a large set of published sequencing data, we observed a long-range power law correlation of DNA methylation with cell class-specific scaling exponents in the range of tens of kilobases. We showed that such cell class-specific scaling exponents are caused by different patchiness of DNA methylation in different cells. By modeling the chromatin structure using high-resolution chromosome conformation capture data and mapping the methylation level onto the modeled structure, we demonstrated that the patchiness of DNA methylation is related to chromatin structure. The scaling exponents of the power law correlation are thus a display of the spatial organization of chromatin. Besides the long-range correlation, we also showed that the local correlation of DNA methylation is associated with nucleosome positioning. The local correlation of partially methylated domains is different from that of nonpartially methylated domains, suggesting that their chromatin structures differ at the scale of several hundred base pairs (covering a few nucleosomes). Our study provides a novel, to our knowledge, view of the spatial organization of chromatin structure from a perspective of DNA methylation, in which both long-range and local correlations of DNA methylation along the genome reflect the spatial organization of chromatin.

@article{
 title = {Structural modeling of chromatin integrates genome features and reveals chromosome folding principle},
 type = {article},
 year = {2017},
 pages = {2818},
 volume = {7},
 publisher = {Springer US},
 id = {a80f2f6d-9148-3708-81ee-88f54732bd55},
 created = {2022-03-08T08:24:59.287Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2023-08-14T21:28:53.557Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Xie2017},
 private_publication = {false},
 abstract = {How chromosomes fold into 3D structures and how genome functions are affected or even controlled by their spatial organization remain challenging questions. Hi-C experiment has provided important structural insights for chromosome, and Hi-C data are used here to construct the 3D chromatin structure which are characterized by two spatially segregated chromatin compartments A and B. By mapping a plethora of genome features onto the constructed 3D chromatin model, we show vividly the close connection between genome properties and the spatial organization of chromatin. We are able to dissect the whole chromatin into two types of chromatin domains which have clearly different Hi-C contact patterns as well as different sizes of chromatin loops. The two chromatin types can be respectively regarded as the basic units of chromatin compartments A and B, and also spatially segregate from each other as the two chromatin compartments. Therefore, the chromatin loops segregate in the space according to their sizes, suggesting the excluded volume or entropic effect in chromatin compartmentalization as well as chromosome positioning. Taken together, these results provide clues to the folding principles of chromosomes, their spatial organization, and the resulted clustering of many genome features in the 3D space.},
 bibtype = {article},
 author = {Xie, Wen Jun and Meng, Luming and Liu, Sirui and Zhang, Ling and Cai, Xiaoxia and Gao, Yi Qin},
 doi = {10.1038/s41598-017-02923-6},
 journal = {Scientific Reports}
}

How chromosomes fold into 3D structures and how genome functions are affected or even controlled by their spatial organization remain challenging questions. Hi-C experiment has provided important structural insights for chromosome, and Hi-C data are used here to construct the 3D chromatin structure which are characterized by two spatially segregated chromatin compartments A and B. By mapping a plethora of genome features onto the constructed 3D chromatin model, we show vividly the close connection between genome properties and the spatial organization of chromatin. We are able to dissect the whole chromatin into two types of chromatin domains which have clearly different Hi-C contact patterns as well as different sizes of chromatin loops. The two chromatin types can be respectively regarded as the basic units of chromatin compartments A and B, and also spatially segregate from each other as the two chromatin compartments. Therefore, the chromatin loops segregate in the space according to their sizes, suggesting the excluded volume or entropic effect in chromatin compartmentalization as well as chromosome positioning. Taken together, these results provide clues to the folding principles of chromosomes, their spatial organization, and the resulted clustering of many genome features in the 3D space.

@article{
 title = {Ion pairing in alkali nitrate electrolyte solutions},
 type = {article},
 year = {2016},
 pages = {2343-2351},
 volume = {120},
 websites = {https://www.ncbi.nlm.nih.gov/pubmed/26901167},
 publisher = {American Chemical Society},
 id = {9e345312-6452-33df-9516-23ef58dc7063},
 created = {2017-09-28T14:05:00.306Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2020-08-12T04:26:58.936Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Xie2016},
 source_type = {Journal Article},
 notes = {Xie, Wen Jun<br/>Zhang, Zhen<br/>Gao, Yi Qin<br/>eng<br/>Research Support, Non-U.S. Gov't<br/>2016/02/24 06:00<br/>J Phys Chem B. 2016 Mar 10;120(9):2343-51. doi: 10.1021/acs.jpcb.5b10755. Epub 2016 Feb 22.},
 private_publication = {false},
 abstract = {In this study, we investigate the thermodynamics of alkali nitrate salt solutions, especially the formation of contact ion pairs between alkali cation and nitrate anion. The ion-pairing propensity shows an order of LiNO3 < NaNO3 < KNO3. Such results explain the salt activity coefficients and suggest that the empirical “law of matching water affinity” is followed by these alkali nitrate salt solutions. The spatial patterns of contact ion pairs are different in the three salt solutions studied here: Li+ forms the contact ion pair with only one oxygen of the nitrate while Na+ and K+ can also be shared by two oxygens of the nitrate. In reproducing the salt activity coefficient using Kirkwood–Buff theory, we find that it is essential to include electronic polarization for Li+ which has a high charge density. The electronic continuum correction for nonpolarizable force field significantly improves the agreement between the calculated activity coefficients and their experimental values. This approach also improv...},
 bibtype = {article},
 author = {Xie, Wen Jun and Zhang, Zhen and Gao, Yi Qin},
 doi = {10.1021/acs.jpcb.5b10755},
 journal = {Journal of Physical Chemistry B}
}

In this study, we investigate the thermodynamics of alkali nitrate salt solutions, especially the formation of contact ion pairs between alkali cation and nitrate anion. The ion-pairing propensity shows an order of LiNO3 < NaNO3 < KNO3. Such results explain the salt activity coefficients and suggest that the empirical “law of matching water affinity” is followed by these alkali nitrate salt solutions. The spatial patterns of contact ion pairs are different in the three salt solutions studied here: Li+ forms the contact ion pair with only one oxygen of the nitrate while Na+ and K+ can also be shared by two oxygens of the nitrate. In reproducing the salt activity coefficient using Kirkwood–Buff theory, we find that it is essential to include electronic polarization for Li+ which has a high charge density. The electronic continuum correction for nonpolarizable force field significantly improves the agreement between the calculated activity coefficients and their experimental values. This approach also improv...

@article{
 title = {Tuning ice nucleation with counterions on polyelectrolyte brush surfaces},
 type = {article},
 year = {2016},
 pages = {e1600345},
 volume = {2},
 websites = {http://advances.sciencemag.org/cgi/doi/10.1126/sciadv.1600345},
 id = {dbdc8176-fe3b-3975-98de-6fcfe7d86fe2},
 created = {2017-09-28T14:05:00.576Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2020-05-11T21:11:29.702Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {He2016},
 source_type = {Journal Article},
 notes = {He, Zhiyuan<br/>Xie, Wen Jun<br/>Liu, Zhenqi<br/>Liu, Guangming<br/>Wang, Zuowei<br/>Gao, Yi Qin<br/>Wang, Jianjun<br/>eng<br/>2016/07/08 06:00<br/>Sci Adv. 2016 Jun 3;2(6):e1600345. doi: 10.1126/sciadv.1600345. eCollection 2016 Jun.},
 private_publication = {false},
 abstract = {Heterogeneous ice nucleation (HIN) on ionic surfaces is ubiquitous in a wide range of atmospheric aerosols and at biological interfaces. Despite its great importance in cirrus cloud formation and cryopreservation of cells, organs, and tissues, it remains unclear whether the ion-specific effect on ice nucleation exists. Benefiting from the fact that ions at the polyelectrolyte brush (PB)/water interface can be reversibly exchanged, we report the effect of ions on HIN on the PB surface, and we discover that the distinct efficiency of ions in tuning HIN follows the Hofmeister series. Moreover, a large HIN temperature window of up to 7.8°C is demonstrated. By establishing a correlation between the fraction of ice-like water molecules and the kinetics of structural transformation from liquid- to ice-like water molecules at the PB/water interface with different counterions, we show that our molecular dynamics simulation analysis is consistent with the experimental observation of the ion-specific effect on HIN.},
 bibtype = {article},
 author = {He, Zhiyuan and Xie, Wen Jun and Liu, Zhenqi and Liu, Guangming and Wang, Zuowei and Gao, Yi Qin and Wang, Jianjun},
 doi = {10.1126/sciadv.1600345},
 journal = {Science Advances}
}

Heterogeneous ice nucleation (HIN) on ionic surfaces is ubiquitous in a wide range of atmospheric aerosols and at biological interfaces. Despite its great importance in cirrus cloud formation and cryopreservation of cells, organs, and tissues, it remains unclear whether the ion-specific effect on ice nucleation exists. Benefiting from the fact that ions at the polyelectrolyte brush (PB)/water interface can be reversibly exchanged, we report the effect of ions on HIN on the PB surface, and we discover that the distinct efficiency of ions in tuning HIN follows the Hofmeister series. Moreover, a large HIN temperature window of up to 7.8°C is demonstrated. By establishing a correlation between the fraction of ice-like water molecules and the kinetics of structural transformation from liquid- to ice-like water molecules at the PB/water interface with different counterions, we show that our molecular dynamics simulation analysis is consistent with the experimental observation of the ion-specific effect on HIN.

@article{
 title = {Dual reorientation relaxation routes of water molecules in oxyanion's hydration shell: A molecular geometry perspective},
 type = {article},
 year = {2015},
 keywords = {ab initio calculations,molecular configurations,molecular dynamics method,negative ions,nitrogen compounds,reaction kinetics theory,solvation,water},
 pages = {224504},
 volume = {143},
 websites = {http://scitation.aip.org/content/aip/journal/jcp/143/22/10.1063/1.4937361,http://scitation.aip.org/docserver/fulltext/aip/journal/jcp/143/22/1.4937361.pdf?expires=1465141751&id=id&accname=2100800&checksum=33F6D79727EBCF767D537976C0A2D868},
 id = {256b7a21-674b-3d8e-9ecf-6c94c55d67e8},
 created = {2017-09-28T14:05:00.442Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2020-08-12T04:26:59.298Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Xie2015},
 source_type = {Journal Article},
 private_publication = {false},
 abstract = {In this study, we examine how complex ions such as oxyanions influence the dynamic properties of water and whether differences exist between simple halide anions and oxyanions. Nitrate anion is taken as an example to investigate the hydration properties of oxyanions. Reorientation relaxation of its hydration water can occur through two different routes: water can either break its hydrogen bond with the nitrate to form one with another water or switch between two oxygen atoms of the same nitrate. The latter molecular mechanism increases the residence time of oxyanion's hydration water and thus nitrate anion slows down the translational motion of neighbouring water. But it is also a "structure breaker" in that it accelerates the reorientation relaxation of hydration water. Such a result illustrates that differences do exist between the hydration of oxyanions and simple halide anions as a result of different molecular geometries. Furthermore, the rotation of the nitrate solute is coupled with the hydrogen bond rearrangement of its hydration water. The nitrate anion can either tilt along the axis perpendicularly to the plane or rotate in the plane. We find that the two reorientation relaxation routes of the hydration water lead to different relaxation dynamics in each of the two above movements of the nitrate solute. The current study suggests that molecular geometry could play an important role in solute hydration and dynamics.},
 bibtype = {article},
 author = {Xie, Wen Jun and Yang, Yi Isaac and Gao, Yi Qin},
 doi = {10.1063/1.4937361},
 journal = {Journal of Chemical Physics}
}

In this study, we examine how complex ions such as oxyanions influence the dynamic properties of water and whether differences exist between simple halide anions and oxyanions. Nitrate anion is taken as an example to investigate the hydration properties of oxyanions. Reorientation relaxation of its hydration water can occur through two different routes: water can either break its hydrogen bond with the nitrate to form one with another water or switch between two oxygen atoms of the same nitrate. The latter molecular mechanism increases the residence time of oxyanion's hydration water and thus nitrate anion slows down the translational motion of neighbouring water. But it is also a "structure breaker" in that it accelerates the reorientation relaxation of hydration water. Such a result illustrates that differences do exist between the hydration of oxyanions and simple halide anions as a result of different molecular geometries. Furthermore, the rotation of the nitrate solute is coupled with the hydrogen bond rearrangement of its hydration water. The nitrate anion can either tilt along the axis perpendicularly to the plane or rotate in the plane. We find that the two reorientation relaxation routes of the hydration water lead to different relaxation dynamics in each of the two above movements of the nitrate solute. The current study suggests that molecular geometry could play an important role in solute hydration and dynamics.

@article{
 title = {DNA cross-triggered cascading self-amplification artificial biochemical circuit},
 type = {article},
 year = {2015},
 keywords = {dual-amplification,enzyme,hybridization chain-reaction,isothermal amplification,micrornas,replication,rna,strand-displacement,ultrasensitive detection},
 pages = {1225-1229},
 volume = {6},
 websites = {http://xlink.rsc.org/?DOI=C4SC03225J},
 id = {884ce6db-6183-3892-8776-2da3e167a420},
 created = {2017-09-28T14:05:00.537Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2020-08-12T04:26:59.125Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Nie2015},
 source_type = {Journal Article},
 language = {English},
 notes = {Az3sn<br/>Times Cited:3<br/>Cited References Count:29},
 private_publication = {false},
 abstract = {The construction of compact and robust artificial biochemical circuits based on nucleic acids can help researchers to understand the essential mechanisms of complex biological systems, and design sophisticated strategies for various requirements. In this study, a novel DNA cross-triggered cascading self-amplification artificial biochemical circuit was developed. Once triggered by trace amounts (as low as 2 amol) of either of two fully independent oligonucleotide factors under homogeneous isothermal conditions, the circuit simultaneously amplified both factors by 105–107 fold, which was proved using mass spectrometry. The compact and robust circuit was successfully used to construct a multi-input Boolean logic operation and a sensitive DNA biosensor based on the dual-amplification of both the target and reporter. The circuit showed great potential for signal gain in complicated molecular programming, and flexible control of nucleic acid nanomachines in biochemical network systems and nanotechnology.},
 bibtype = {article},
 author = {Nie, Ji and Zhao, Ming-Zhe and Xie, Wen Jun and Cai, Liang-Yuan and Zhou, Ying-Lin and Zhang, Xin-Xiang},
 doi = {10.1039/C4SC03225J},
 journal = {Chemical Science}
}

The construction of compact and robust artificial biochemical circuits based on nucleic acids can help researchers to understand the essential mechanisms of complex biological systems, and design sophisticated strategies for various requirements. In this study, a novel DNA cross-triggered cascading self-amplification artificial biochemical circuit was developed. Once triggered by trace amounts (as low as 2 amol) of either of two fully independent oligonucleotide factors under homogeneous isothermal conditions, the circuit simultaneously amplified both factors by 105–107 fold, which was proved using mass spectrometry. The compact and robust circuit was successfully used to construct a multi-input Boolean logic operation and a sensitive DNA biosensor based on the dual-amplification of both the target and reporter. The circuit showed great potential for signal gain in complicated molecular programming, and flexible control of nucleic acid nanomachines in biochemical network systems and nanotechnology.

@article{
 title = {On the molecular mechanism of ion specific Hofmeister series},
 type = {article},
 year = {2014},
 keywords = {Hofmeister series,hydrogen donor/acceptor equilibrium,ion cooperativity,protein denaturant,protein protectant,salt effects,surface tension},
 pages = {36-47},
 volume = {57},
 websites = {http://download.springer.com/static/pdf/815/art%253A10.1007%252Fs11426-013-5019-1.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs11426-013-5019-1&token2=exp=1465142065~acl=%2Fstatic%2Fpdf%2F815%2Fart%25253A10.1007%25252Fs11426-013-501},
 id = {1030642d-1819-3a70-b9bf-c95e9323d3dd},
 created = {2017-09-28T14:05:00.489Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2020-08-12T04:26:59.143Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Xie2014},
 source_type = {Journal Article},
 language = {English},
 notes = {Sp. Iss. SI<br/>281OE<br/>Times Cited:6<br/>Cited References Count:99},
 private_publication = {false},
 abstract = {Hofmeister series ranks the ability of salt ions in influencing a\nvariety of properties and processes in aqueous solutions. In this\nreview, we reexamine how these ions and some other small molecules\naffect water structure and thermodynamic properties, such as surface\ntension and protein backbone solvation. We illustrate the difficulties\nin interpreting the thermodynamic information based on structural and\ndynamic arguments. As an alternative, we show that the solvation\nproperties of ions and proteins/small molecules can be used to explain\nthe salt effects on the thermodynamic properties of the solutions. Our\nanalysis shows that the often neglected cation-anion cooperativity plays\na very important role in these effects. We also argue that the change of\nhydrogen donor/acceptor equilibrium by added cosolutes/cosolvents can be\nused to explain their effects on protein secondary structure\ndenaturation/protection: those increase hydrogen donor concentrations\nsuch as urea and salts with strongly solvated cations/weakly hydrated\nanions tend to dissolve protein backbone acting as secondary structure\ndenaturants, whereas those lack of hydrogen donors but rich in acceptors\nhave the opposite effect.},
 bibtype = {article},
 author = {Xie, Wen Jun and Liu, Chengwen and Yang, Lijiang and Gao, Yi Qin},
 doi = {10.1007/s11426-013-5019-1},
 journal = {Science China Chemistry}
}

Hofmeister series ranks the ability of salt ions in influencing a\nvariety of properties and processes in aqueous solutions. In this\nreview, we reexamine how these ions and some other small molecules\naffect water structure and thermodynamic properties, such as surface\ntension and protein backbone solvation. We illustrate the difficulties\nin interpreting the thermodynamic information based on structural and\ndynamic arguments. As an alternative, we show that the solvation\nproperties of ions and proteins/small molecules can be used to explain\nthe salt effects on the thermodynamic properties of the solutions. Our\nanalysis shows that the often neglected cation-anion cooperativity plays\na very important role in these effects. We also argue that the change of\nhydrogen donor/acceptor equilibrium by added cosolutes/cosolvents can be\nused to explain their effects on protein secondary structure\ndenaturation/protection: those increase hydrogen donor concentrations\nsuch as urea and salts with strongly solvated cations/weakly hydrated\nanions tend to dissolve protein backbone acting as secondary structure\ndenaturants, whereas those lack of hydrogen donors but rich in acceptors\nhave the opposite effect.

@article{
 title = {A simple theory for the Hofmeister series},
 type = {article},
 year = {2013},
 keywords = {aqueous guanidinium chloride,bubble coalescence,hydration,hydrogen-bonds,ion cooperativity,molecular-dynamics,proteins,salt-solutions,surface-tension,water-surface},
 pages = {4247−4252},
 volume = {4},
 websites = {http://pubs.acs.org/doi/pdfplus/10.1021/jz402072g},
 id = {b846131f-9b61-31eb-b356-23dfa1fc9c64},
 created = {2017-09-28T14:05:00.307Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2022-12-21T02:31:48.360Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Xie2013},
 source_type = {Journal Article},
 language = {English},
 notes = {278WN<br/>Times Cited:13<br/>Cited References Count:42},
 private_publication = {false},
 abstract = {In cells, biological molecules function in an aqueous solution. Electrolytes and other small molecules play important roles in keeping the osmotic pressure of the cellular environment as well as the structure formation and function of biomolecules. The observed empirical rules such as Hofmeister series are still waiting for molecular interpretations. In this Perspective, we will discuss a simple and self-consistent theory that takes into account the cooperative effects of cations and anions in affecting water/air surface tension, water activity, and the solubility of model compounds including polypeptides. Molecular dynamics simulations used to test these theoretical models will also be discussed.},
 bibtype = {article},
 author = {Xie, Wen Jun and Gao, Yi Qin},
 doi = {Doi 10.1021/Jz402072g},
 journal = {Journal of Physical Chemistry Letters}
}

In cells, biological molecules function in an aqueous solution. Electrolytes and other small molecules play important roles in keeping the osmotic pressure of the cellular environment as well as the structure formation and function of biomolecules. The observed empirical rules such as Hofmeister series are still waiting for molecular interpretations. In this Perspective, we will discuss a simple and self-consistent theory that takes into account the cooperative effects of cations and anions in affecting water/air surface tension, water activity, and the solubility of model compounds including polypeptides. Molecular dynamics simulations used to test these theoretical models will also be discussed.

@article{
 title = {Microscopic origin of the deviation from stokes-einstein behavior observed in dynamics of the KSCN aqueous solutions: A MD simulation study},
 type = {article},
 year = {2013},
 keywords = {chloride solutions,cluster formation,electrolyte-solutions,hydrogen-bond kinetics,liquid water,molecular-dynamics,osmotic coefficients,rotational diffusion,vibrational-energy transfer,water reorientation},
 pages = {2992-3004},
 volume = {117},
 websites = {http://pubs.acs.org/doi/pdfplus/10.1021/jp400441e},
 id = {4abcbfbd-2aee-3ab1-98a8-375246ce45e3},
 created = {2017-09-28T14:05:00.347Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2020-08-12T04:26:58.941Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Zhang2013},
 source_type = {Journal Article},
 language = {English},
 notes = {108PP<br/>Times Cited:14<br/>Cited References Count:94},
 private_publication = {false},
 abstract = {Molecular dynamics simulations were carried out to investigate the microscopic origin of the deviation from Stokes-Einstein behavior observed in the dynamics of KSCN aqueous solutions. When the solution becomes more concentrated, the rotational mobilities of SCN- and water bifurcate significantly as also observed in the experimental ultrafast infrared measurements. The translational mobilities of different components, on the other hand, have similar concentration dependences. Furthermore, when concentrating the solution, the mobilities increase slightly first and then reduce afterward. Our simulations revealed that these phenomena observed in the dynamics originate from the ion assembling in the solution. The RDF and pair residence time analysis further suggest the ion pairing effect has significant contribution to the ion assembling. Results herein thus provide a microscopic insight on the origin of the ion assembling phenomenon and its connection with various experimentally observable dynamical phenomena in the ionic solutions.},
 bibtype = {article},
 author = {Zhang, Qiang and Xie, Wen Jun and Bian, Hongtao and Gao, Yi Qin and Zheng, Junrong and Zhuang, Wei},
 doi = {10.1021/jp400441e},
 journal = {Journal of Physical Chemistry B}
}

Molecular dynamics simulations were carried out to investigate the microscopic origin of the deviation from Stokes-Einstein behavior observed in the dynamics of KSCN aqueous solutions. When the solution becomes more concentrated, the rotational mobilities of SCN- and water bifurcate significantly as also observed in the experimental ultrafast infrared measurements. The translational mobilities of different components, on the other hand, have similar concentration dependences. Furthermore, when concentrating the solution, the mobilities increase slightly first and then reduce afterward. Our simulations revealed that these phenomena observed in the dynamics originate from the ion assembling in the solution. The RDF and pair residence time analysis further suggest the ion pairing effect has significant contribution to the ion assembling. Results herein thus provide a microscopic insight on the origin of the ion assembling phenomenon and its connection with various experimentally observable dynamical phenomena in the ionic solutions.

@article{
 title = {Ion cooperativity and the effect of salts on polypeptide structure – a molecular dynamics study of BBA5 in salt solutions},
 type = {article},
 year = {2013},
 pages = {191-206},
 volume = {160},
 websites = {http://xlink.rsc.org/?DOI=C2FD20065A},
 publisher = {The Royal Society of Chemistry},
 id = {daaa5a27-a332-3acd-aa89-42929105183a},
 created = {2017-09-28T14:05:00.670Z},
 file_attached = {true},
 profile_id = {7caa5d1e-e498-3efc-950d-2841e4174da7},
 last_modified = {2020-08-12T04:26:59.168Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Xie2013a},
 source_type = {Journal Article},
 private_publication = {false},
 abstract = {Using molecular dynamics simulations, we investigated effects of inorganic salts on the structure and dynamics of a short [small alpha],[small beta]-polypeptide, BBA5. The simulations showed that three model salts, NaI, NaF, and Na2SO3, have very different effects on the structure of the polypeptide. The addition of NaI to the aqueous solution caused denaturation and significantly weakened hydrogen bonds of the polypeptide. Na2SO3 strengthened the hydrophobic interactions and increased hydrogen bonding of the polypeptide. Preferred binding of Na+ to the backbone carbonyl groups of BBA5 occurred in the NaI solution, consistent with the weakened protein backbone hydrogen bonds, whereas Na+ is excluded more from the vicinity of the protein backbone in the Na2SO3 solution. This difference in Na+ binding correlates well with the different propensities of the counter ions approaching the protein surface: SO32- is much more strongly expelled from the protein apolar surface than I-, and demonstrates the importance of cation-anion cooperativity in affecting protein structures. The binding of the two salts to and their effects on the hydration of the protein surface depends strongly on the polarity of the latter. However, both salts reduce the flexibility of the polypeptide and the fluctuation of its hydration layer. These simulations showed that the chaotropic NaI affects protein structure mainly through a direct binding of Na+ to the backbone and I- to the protein surface. The main effect of Na2SO3 manifests in strengthening the hydrophobic interaction and consequently the hydrogen bonding of the protein, more likely through an "indirect" mechanism. In addition, the simulations showed that NaF has a similar effect as Na2SO3 (but weaker than the latter, consistent with their positions in the Hofmeister series).},
 bibtype = {article},
 author = {Xie, Wen Jun and Gao, Yi Qin},
 doi = {10.1039/C2FD20065A},
 journal = {Faraday Discussions}
}

Using molecular dynamics simulations, we investigated effects of inorganic salts on the structure and dynamics of a short [small alpha],[small beta]-polypeptide, BBA5. The simulations showed that three model salts, NaI, NaF, and Na2SO3, have very different effects on the structure of the polypeptide. The addition of NaI to the aqueous solution caused denaturation and significantly weakened hydrogen bonds of the polypeptide. Na2SO3 strengthened the hydrophobic interactions and increased hydrogen bonding of the polypeptide. Preferred binding of Na+ to the backbone carbonyl groups of BBA5 occurred in the NaI solution, consistent with the weakened protein backbone hydrogen bonds, whereas Na+ is excluded more from the vicinity of the protein backbone in the Na2SO3 solution. This difference in Na+ binding correlates well with the different propensities of the counter ions approaching the protein surface: SO32- is much more strongly expelled from the protein apolar surface than I-, and demonstrates the importance of cation-anion cooperativity in affecting protein structures. The binding of the two salts to and their effects on the hydration of the protein surface depends strongly on the polarity of the latter. However, both salts reduce the flexibility of the polypeptide and the fluctuation of its hydration layer. These simulations showed that the chaotropic NaI affects protein structure mainly through a direct binding of Na+ to the backbone and I- to the protein surface. The main effect of Na2SO3 manifests in strengthening the hydrophobic interaction and consequently the hydrogen bonding of the protein, more likely through an "indirect" mechanism. In addition, the simulations showed that NaF has a similar effect as Na2SO3 (but weaker than the latter, consistent with their positions in the Hofmeister series).