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Flexible Gaussian Accelerated Molecular Dynamics to Enhance Biological Sampling

[Image: see text] Molecular dynamics simulations often struggle to obtain sufficient sampling to study complex molecular events due to high energy barriers separating the minima of interest. Multiple enhanced sampling techniques have been developed and improved over the years to tackle this issue. G...

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Autores principales: Gracia Carmona, Oriol, Oostenbrink, Chris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536968/
https://www.ncbi.nlm.nih.gov/pubmed/37649349
http://dx.doi.org/10.1021/acs.jctc.3c00619
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author Gracia Carmona, Oriol
Oostenbrink, Chris
author_facet Gracia Carmona, Oriol
Oostenbrink, Chris
author_sort Gracia Carmona, Oriol
collection PubMed
description [Image: see text] Molecular dynamics simulations often struggle to obtain sufficient sampling to study complex molecular events due to high energy barriers separating the minima of interest. Multiple enhanced sampling techniques have been developed and improved over the years to tackle this issue. Gaussian accelerated molecular dynamics (GaMD) is a recently developed enhanced sampling technique that works by adding a biasing potential, lifting the energy landscape up, and decreasing the height of its barriers. GaMD allows one to increase the sampling of events of interest without the need of a priori knowledge of the system or the relevant coordinates. All required acceleration parameters can be obtained from a previous search run. Upon its development, several improvements for the methodology have been proposed, among them selective GaMD in which the boosting potential is selectively applied to the region of interest. There are currently four selective GaMD methods that have shown promising results. However, all of these methods are constrained on the number, location, and scenarios in which this selective boosting potential can be applied to ligands, peptides, or protein–protein interactions. In this work, we showcase a GROMOS implementation of the GaMD methodology with a fully flexible selective GaMD approach that allows the user to define, in a straightforward way, multiple boosting potentials for as many regions as desired. We show and analyze the advantages of this flexible selective approach on two previously used test systems, the alanine dipeptide and the chignolin peptide, and extend these examples to study its applicability and potential to study conformational changes of glycans and glycosylated proteins.
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spelling pubmed-105369682023-09-29 Flexible Gaussian Accelerated Molecular Dynamics to Enhance Biological Sampling Gracia Carmona, Oriol Oostenbrink, Chris J Chem Theory Comput [Image: see text] Molecular dynamics simulations often struggle to obtain sufficient sampling to study complex molecular events due to high energy barriers separating the minima of interest. Multiple enhanced sampling techniques have been developed and improved over the years to tackle this issue. Gaussian accelerated molecular dynamics (GaMD) is a recently developed enhanced sampling technique that works by adding a biasing potential, lifting the energy landscape up, and decreasing the height of its barriers. GaMD allows one to increase the sampling of events of interest without the need of a priori knowledge of the system or the relevant coordinates. All required acceleration parameters can be obtained from a previous search run. Upon its development, several improvements for the methodology have been proposed, among them selective GaMD in which the boosting potential is selectively applied to the region of interest. There are currently four selective GaMD methods that have shown promising results. However, all of these methods are constrained on the number, location, and scenarios in which this selective boosting potential can be applied to ligands, peptides, or protein–protein interactions. In this work, we showcase a GROMOS implementation of the GaMD methodology with a fully flexible selective GaMD approach that allows the user to define, in a straightforward way, multiple boosting potentials for as many regions as desired. We show and analyze the advantages of this flexible selective approach on two previously used test systems, the alanine dipeptide and the chignolin peptide, and extend these examples to study its applicability and potential to study conformational changes of glycans and glycosylated proteins. American Chemical Society 2023-08-31 /pmc/articles/PMC10536968/ /pubmed/37649349 http://dx.doi.org/10.1021/acs.jctc.3c00619 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Gracia Carmona, Oriol
Oostenbrink, Chris
Flexible Gaussian Accelerated Molecular Dynamics to Enhance Biological Sampling
title Flexible Gaussian Accelerated Molecular Dynamics to Enhance Biological Sampling
title_full Flexible Gaussian Accelerated Molecular Dynamics to Enhance Biological Sampling
title_fullStr Flexible Gaussian Accelerated Molecular Dynamics to Enhance Biological Sampling
title_full_unstemmed Flexible Gaussian Accelerated Molecular Dynamics to Enhance Biological Sampling
title_short Flexible Gaussian Accelerated Molecular Dynamics to Enhance Biological Sampling
title_sort flexible gaussian accelerated molecular dynamics to enhance biological sampling
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536968/
https://www.ncbi.nlm.nih.gov/pubmed/37649349
http://dx.doi.org/10.1021/acs.jctc.3c00619
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