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Optimization of Protein Backbone Dihedral Angles by Means of Hamiltonian Reweighting
[Image: see text] Molecular dynamics simulations depend critically on the accuracy of the underlying force fields in properly representing biomolecules. Hence, it is crucial to validate the force-field parameter sets in this respect. In the context of the GROMOS force field, this is usually achieved...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039763/ https://www.ncbi.nlm.nih.gov/pubmed/27559757 http://dx.doi.org/10.1021/acs.jcim.6b00399 |
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author | Margreitter, Christian Oostenbrink, Chris |
author_facet | Margreitter, Christian Oostenbrink, Chris |
author_sort | Margreitter, Christian |
collection | PubMed |
description | [Image: see text] Molecular dynamics simulations depend critically on the accuracy of the underlying force fields in properly representing biomolecules. Hence, it is crucial to validate the force-field parameter sets in this respect. In the context of the GROMOS force field, this is usually achieved by comparing simulation data to experimental observables for small molecules. In this study, we develop new amino acid backbone dihedral angle potential energy parameters based on the widely used 54A7 parameter set by matching to experimental J values and secondary structure propensity scales. In order to find the most appropriate backbone parameters, close to 100 000 different combinations of parameters have been screened. However, since the sheer number of combinations considered prohibits actual molecular dynamics simulations for each of them, we instead predicted the values for every combination using Hamiltonian reweighting. While the original 54A7 parameter set fails to reproduce the experimental data, we are able to provide parameters that match significantly better. However, to ensure applicability in the context of larger peptides and full proteins, further studies have to be undertaken. |
format | Online Article Text |
id | pubmed-5039763 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-50397632016-09-29 Optimization of Protein Backbone Dihedral Angles by Means of Hamiltonian Reweighting Margreitter, Christian Oostenbrink, Chris J Chem Inf Model [Image: see text] Molecular dynamics simulations depend critically on the accuracy of the underlying force fields in properly representing biomolecules. Hence, it is crucial to validate the force-field parameter sets in this respect. In the context of the GROMOS force field, this is usually achieved by comparing simulation data to experimental observables for small molecules. In this study, we develop new amino acid backbone dihedral angle potential energy parameters based on the widely used 54A7 parameter set by matching to experimental J values and secondary structure propensity scales. In order to find the most appropriate backbone parameters, close to 100 000 different combinations of parameters have been screened. However, since the sheer number of combinations considered prohibits actual molecular dynamics simulations for each of them, we instead predicted the values for every combination using Hamiltonian reweighting. While the original 54A7 parameter set fails to reproduce the experimental data, we are able to provide parameters that match significantly better. However, to ensure applicability in the context of larger peptides and full proteins, further studies have to be undertaken. American Chemical Society 2016-08-25 2016-09-26 /pmc/articles/PMC5039763/ /pubmed/27559757 http://dx.doi.org/10.1021/acs.jcim.6b00399 Text en Copyright © 2016 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
spellingShingle | Margreitter, Christian Oostenbrink, Chris Optimization of Protein Backbone Dihedral Angles by Means of Hamiltonian Reweighting |
title | Optimization of Protein Backbone Dihedral Angles by
Means of Hamiltonian Reweighting |
title_full | Optimization of Protein Backbone Dihedral Angles by
Means of Hamiltonian Reweighting |
title_fullStr | Optimization of Protein Backbone Dihedral Angles by
Means of Hamiltonian Reweighting |
title_full_unstemmed | Optimization of Protein Backbone Dihedral Angles by
Means of Hamiltonian Reweighting |
title_short | Optimization of Protein Backbone Dihedral Angles by
Means of Hamiltonian Reweighting |
title_sort | optimization of protein backbone dihedral angles by
means of hamiltonian reweighting |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039763/ https://www.ncbi.nlm.nih.gov/pubmed/27559757 http://dx.doi.org/10.1021/acs.jcim.6b00399 |
work_keys_str_mv | AT margreitterchristian optimizationofproteinbackbonedihedralanglesbymeansofhamiltonianreweighting AT oostenbrinkchris optimizationofproteinbackbonedihedralanglesbymeansofhamiltonianreweighting |