OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations

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dc.citation.articleNumbere1008308en_US
dc.citation.issueNumber2en_US
dc.citation.journalTitlePLOS Computational Biologyen_US
dc.citation.volumeNumber17en_US
dc.contributor.authorLu, Weien_US
dc.contributor.authorBueno, Carlosen_US
dc.contributor.authorSchafer, Nicholas P.en_US
dc.contributor.authorMoller, Joshuaen_US
dc.contributor.authorJin, Shikaien_US
dc.contributor.authorChen, Xunen_US
dc.contributor.authorChen, Mingchenen_US
dc.contributor.authorGu, Xinyuen_US
dc.contributor.authorDavtyan, Aramen_US
dc.contributor.authorPablo, Juan J. deen_US
dc.contributor.authorWolynes, Peter G.en_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2021-04-21T15:46:22Zen_US
dc.date.available2021-04-21T15:46:22Zen_US
dc.date.issued2021en_US
dc.description.abstractWe present OpenAWSEM and Open3SPN2, new cross-compatible implementations of coarse-grained models for protein (AWSEM) and DNA (3SPN2) molecular dynamics simulations within the OpenMM framework. These new implementations retain the chemical accuracy and intrinsic efficiency of the original models while adding GPU acceleration and the ease of forcefield modification provided by OpenMM’s Custom Forces software framework. By utilizing GPUs, we achieve around a 30-fold speedup in protein and protein-DNA simulations over the existing LAMMPS-based implementations running on a single CPU core. We showcase the benefits of OpenMM’s Custom Forces framework by devising and implementing two new potentials that allow us to address important aspects of protein folding and structure prediction and by testing the ability of the combined OpenAWSEM and Open3SPN2 to model protein-DNA binding. The first potential is used to describe the changes in effective interactions that occur as a protein becomes partially buried in a membrane. We also introduced an interaction to describe proteins with multiple disulfide bonds. Using simple pairwise disulfide bonding terms results in unphysical clustering of cysteine residues, posing a problem when simulating the folding of proteins with many cysteines. We now can computationally reproduce Anfinsen’s early Nobel prize winning experiments by using OpenMM’s Custom Forces framework to introduce a multi-body disulfide bonding term that prevents unphysical clustering. Our protein-DNA simulations show that the binding landscape is funneled towards structures that are quite similar to those found using experiments. In summary, this paper provides a simulation tool for the molecular biophysics community that is both easy to use and sufficiently efficient to simulate large proteins and large protein-DNA systems that are central to many cellular processes. These codes should facilitate the interplay between molecular simulations and cellular studies, which have been hampered by the large mismatch between the time and length scales accessible to molecular simulations and those relevant to cell biology.en_US
dc.identifier.citationLu, Wei, Bueno, Carlos, Schafer, Nicholas P., et al.. "OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations." <i>PLOS Computational Biology,</i> 17, no. 2 (2021) Public Library of Science: https://doi.org/10.1371/journal.pcbi.1008308.en_US
dc.identifier.digitaljournal-pcbi-1008308en_US
dc.identifier.doihttps://doi.org/10.1371/journal.pcbi.1008308en_US
dc.identifier.urihttps://hdl.handle.net/1911/110303en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleOpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulationsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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