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Study on the Application of the Combination of TMD Simulation and Umbrella Sampling in PMF Calculation for Molecular Conformational Transitions
Free energy calculations of the potential of mean force (PMF) based on the combination of targeted molecular dynamics (TMD) simulations and umbrella samplings as a function of physical coordinates have been applied to explore the detailed pathways and the corresponding free energy profiles for the c...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881518/ https://www.ncbi.nlm.nih.gov/pubmed/27171075 http://dx.doi.org/10.3390/ijms17050692 |
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author | Wang, Qing Xue, Tuo Song, Chunnian Wang, Yan Chen, Guangju |
author_facet | Wang, Qing Xue, Tuo Song, Chunnian Wang, Yan Chen, Guangju |
author_sort | Wang, Qing |
collection | PubMed |
description | Free energy calculations of the potential of mean force (PMF) based on the combination of targeted molecular dynamics (TMD) simulations and umbrella samplings as a function of physical coordinates have been applied to explore the detailed pathways and the corresponding free energy profiles for the conformational transition processes of the butane molecule and the 35-residue villin headpiece subdomain (HP35). The accurate PMF profiles for describing the dihedral rotation of butane under both coordinates of dihedral rotation and root mean square deviation (RMSD) variation were obtained based on the different umbrella samplings from the same TMD simulations. The initial structures for the umbrella samplings can be conveniently selected from the TMD trajectories. For the application of this computational method in the unfolding process of the HP35 protein, the PMF calculation along with the coordinate of the radius of gyration (R(g)) presents the gradual increase of free energies by about 1 kcal/mol with the energy fluctuations. The feature of conformational transition for the unfolding process of the HP35 protein shows that the spherical structure extends and the middle α-helix unfolds firstly, followed by the unfolding of other α-helices. The computational method for the PMF calculations based on the combination of TMD simulations and umbrella samplings provided a valuable strategy in investigating detailed conformational transition pathways for other allosteric processes. |
format | Online Article Text |
id | pubmed-4881518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-48815182016-05-27 Study on the Application of the Combination of TMD Simulation and Umbrella Sampling in PMF Calculation for Molecular Conformational Transitions Wang, Qing Xue, Tuo Song, Chunnian Wang, Yan Chen, Guangju Int J Mol Sci Article Free energy calculations of the potential of mean force (PMF) based on the combination of targeted molecular dynamics (TMD) simulations and umbrella samplings as a function of physical coordinates have been applied to explore the detailed pathways and the corresponding free energy profiles for the conformational transition processes of the butane molecule and the 35-residue villin headpiece subdomain (HP35). The accurate PMF profiles for describing the dihedral rotation of butane under both coordinates of dihedral rotation and root mean square deviation (RMSD) variation were obtained based on the different umbrella samplings from the same TMD simulations. The initial structures for the umbrella samplings can be conveniently selected from the TMD trajectories. For the application of this computational method in the unfolding process of the HP35 protein, the PMF calculation along with the coordinate of the radius of gyration (R(g)) presents the gradual increase of free energies by about 1 kcal/mol with the energy fluctuations. The feature of conformational transition for the unfolding process of the HP35 protein shows that the spherical structure extends and the middle α-helix unfolds firstly, followed by the unfolding of other α-helices. The computational method for the PMF calculations based on the combination of TMD simulations and umbrella samplings provided a valuable strategy in investigating detailed conformational transition pathways for other allosteric processes. MDPI 2016-05-09 /pmc/articles/PMC4881518/ /pubmed/27171075 http://dx.doi.org/10.3390/ijms17050692 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Qing Xue, Tuo Song, Chunnian Wang, Yan Chen, Guangju Study on the Application of the Combination of TMD Simulation and Umbrella Sampling in PMF Calculation for Molecular Conformational Transitions |
title | Study on the Application of the Combination of TMD Simulation and Umbrella Sampling in PMF Calculation for Molecular Conformational Transitions |
title_full | Study on the Application of the Combination of TMD Simulation and Umbrella Sampling in PMF Calculation for Molecular Conformational Transitions |
title_fullStr | Study on the Application of the Combination of TMD Simulation and Umbrella Sampling in PMF Calculation for Molecular Conformational Transitions |
title_full_unstemmed | Study on the Application of the Combination of TMD Simulation and Umbrella Sampling in PMF Calculation for Molecular Conformational Transitions |
title_short | Study on the Application of the Combination of TMD Simulation and Umbrella Sampling in PMF Calculation for Molecular Conformational Transitions |
title_sort | study on the application of the combination of tmd simulation and umbrella sampling in pmf calculation for molecular conformational transitions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881518/ https://www.ncbi.nlm.nih.gov/pubmed/27171075 http://dx.doi.org/10.3390/ijms17050692 |
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