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pmx: Automated protein structure and topology generation for alchemical perturbations

Computational protein design requires methods to accurately estimate free energy changes in protein stability or binding upon an amino acid mutation. From the different approaches available, molecular dynamics-based alchemical free energy calculations are unique in their accuracy and solid theoretic...

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Autores principales: Gapsys, Vytautas, Michielssens, Servaas, Seeliger, Daniel, de Groot, Bert L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365728/
https://www.ncbi.nlm.nih.gov/pubmed/25487359
http://dx.doi.org/10.1002/jcc.23804
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author Gapsys, Vytautas
Michielssens, Servaas
Seeliger, Daniel
de Groot, Bert L
author_facet Gapsys, Vytautas
Michielssens, Servaas
Seeliger, Daniel
de Groot, Bert L
author_sort Gapsys, Vytautas
collection PubMed
description Computational protein design requires methods to accurately estimate free energy changes in protein stability or binding upon an amino acid mutation. From the different approaches available, molecular dynamics-based alchemical free energy calculations are unique in their accuracy and solid theoretical basis. The challenge in using these methods lies in the need to generate hybrid structures and topologies representing two physical states of a system. A custom made hybrid topology may prove useful for a particular mutation of interest, however, a high throughput mutation analysis calls for a more general approach. In this work, we present an automated procedure to generate hybrid structures and topologies for the amino acid mutations in all commonly used force fields. The described software is compatible with the Gromacs simulation package. The mutation libraries are readily supported for five force fields, namely Amber99SB, Amber99SB*-ILDN, OPLS-AA/L, Charmm22*, and Charmm36.
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spelling pubmed-43657282015-03-23 pmx: Automated protein structure and topology generation for alchemical perturbations Gapsys, Vytautas Michielssens, Servaas Seeliger, Daniel de Groot, Bert L J Comput Chem Software News and Updates Computational protein design requires methods to accurately estimate free energy changes in protein stability or binding upon an amino acid mutation. From the different approaches available, molecular dynamics-based alchemical free energy calculations are unique in their accuracy and solid theoretical basis. The challenge in using these methods lies in the need to generate hybrid structures and topologies representing two physical states of a system. A custom made hybrid topology may prove useful for a particular mutation of interest, however, a high throughput mutation analysis calls for a more general approach. In this work, we present an automated procedure to generate hybrid structures and topologies for the amino acid mutations in all commonly used force fields. The described software is compatible with the Gromacs simulation package. The mutation libraries are readily supported for five force fields, namely Amber99SB, Amber99SB*-ILDN, OPLS-AA/L, Charmm22*, and Charmm36. BlackWell Publishing Ltd 2015-02-15 2014-12-08 /pmc/articles/PMC4365728/ /pubmed/25487359 http://dx.doi.org/10.1002/jcc.23804 Text en © 2014 The Authors Journal of Computational Chemistry Published by Wiley Periodicals, Inc. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Software News and Updates
Gapsys, Vytautas
Michielssens, Servaas
Seeliger, Daniel
de Groot, Bert L
pmx: Automated protein structure and topology generation for alchemical perturbations
title pmx: Automated protein structure and topology generation for alchemical perturbations
title_full pmx: Automated protein structure and topology generation for alchemical perturbations
title_fullStr pmx: Automated protein structure and topology generation for alchemical perturbations
title_full_unstemmed pmx: Automated protein structure and topology generation for alchemical perturbations
title_short pmx: Automated protein structure and topology generation for alchemical perturbations
title_sort pmx: automated protein structure and topology generation for alchemical perturbations
topic Software News and Updates
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365728/
https://www.ncbi.nlm.nih.gov/pubmed/25487359
http://dx.doi.org/10.1002/jcc.23804
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