Cargando…

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

We 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 whi...

Descripción completa

Detalles Bibliográficos
Autores principales: Lu, Wei, Bueno, Carlos, Schafer, Nicholas P., Moller, Joshua, Jin, Shikai, Chen, Xun, Chen, Mingchen, Gu, Xinyu, Davtyan, Aram, de Pablo, Juan J., Wolynes, Peter G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906472/
https://www.ncbi.nlm.nih.gov/pubmed/33577557
http://dx.doi.org/10.1371/journal.pcbi.1008308
_version_ 1783655295666356224
author Lu, Wei
Bueno, Carlos
Schafer, Nicholas P.
Moller, Joshua
Jin, Shikai
Chen, Xun
Chen, Mingchen
Gu, Xinyu
Davtyan, Aram
de Pablo, Juan J.
Wolynes, Peter G.
author_facet Lu, Wei
Bueno, Carlos
Schafer, Nicholas P.
Moller, Joshua
Jin, Shikai
Chen, Xun
Chen, Mingchen
Gu, Xinyu
Davtyan, Aram
de Pablo, Juan J.
Wolynes, Peter G.
author_sort Lu, Wei
collection PubMed
description We 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.
format Online
Article
Text
id pubmed-7906472
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-79064722021-03-03 OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations Lu, Wei Bueno, Carlos Schafer, Nicholas P. Moller, Joshua Jin, Shikai Chen, Xun Chen, Mingchen Gu, Xinyu Davtyan, Aram de Pablo, Juan J. Wolynes, Peter G. PLoS Comput Biol Research Article We 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. Public Library of Science 2021-02-12 /pmc/articles/PMC7906472/ /pubmed/33577557 http://dx.doi.org/10.1371/journal.pcbi.1008308 Text en © 2021 Lu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lu, Wei
Bueno, Carlos
Schafer, Nicholas P.
Moller, Joshua
Jin, Shikai
Chen, Xun
Chen, Mingchen
Gu, Xinyu
Davtyan, Aram
de Pablo, Juan J.
Wolynes, Peter G.
OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations
title OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations
title_full OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations
title_fullStr OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations
title_full_unstemmed OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations
title_short OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations
title_sort openawsem with open3spn2: a fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906472/
https://www.ncbi.nlm.nih.gov/pubmed/33577557
http://dx.doi.org/10.1371/journal.pcbi.1008308
work_keys_str_mv AT luwei openawsemwithopen3spn2afastflexibleandaccessibleframeworkforlargescalecoarsegrainedbiomolecularsimulations
AT buenocarlos openawsemwithopen3spn2afastflexibleandaccessibleframeworkforlargescalecoarsegrainedbiomolecularsimulations
AT schafernicholasp openawsemwithopen3spn2afastflexibleandaccessibleframeworkforlargescalecoarsegrainedbiomolecularsimulations
AT mollerjoshua openawsemwithopen3spn2afastflexibleandaccessibleframeworkforlargescalecoarsegrainedbiomolecularsimulations
AT jinshikai openawsemwithopen3spn2afastflexibleandaccessibleframeworkforlargescalecoarsegrainedbiomolecularsimulations
AT chenxun openawsemwithopen3spn2afastflexibleandaccessibleframeworkforlargescalecoarsegrainedbiomolecularsimulations
AT chenmingchen openawsemwithopen3spn2afastflexibleandaccessibleframeworkforlargescalecoarsegrainedbiomolecularsimulations
AT guxinyu openawsemwithopen3spn2afastflexibleandaccessibleframeworkforlargescalecoarsegrainedbiomolecularsimulations
AT davtyanaram openawsemwithopen3spn2afastflexibleandaccessibleframeworkforlargescalecoarsegrainedbiomolecularsimulations
AT depablojuanj openawsemwithopen3spn2afastflexibleandaccessibleframeworkforlargescalecoarsegrainedbiomolecularsimulations
AT wolynespeterg openawsemwithopen3spn2afastflexibleandaccessibleframeworkforlargescalecoarsegrainedbiomolecularsimulations