Cargando…

Combination of coarse-grained molecular dynamics simulations and small-angle X-ray scattering experiments

The combination of molecular dynamics (MD) simulations and small-angle X-ray scattering (SAXS), called the MD-SAXS method, is efficient for investigating protein dynamics. To overcome the time-scale limitation of all-atom MD simulations, coarse-grained (CG) representations are often utilized for bio...

Descripción completa

Detalles Bibliográficos
Autores principales: Ekimoto, Toru, Kokabu, Yuichi, Oroguchi, Tomotaka, Ikeguchi, Mitsunori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Biophysical Society of Japan (BSJ) 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976007/
https://www.ncbi.nlm.nih.gov/pubmed/31984192
http://dx.doi.org/10.2142/biophysico.16.0_377
_version_ 1783490308289331200
author Ekimoto, Toru
Kokabu, Yuichi
Oroguchi, Tomotaka
Ikeguchi, Mitsunori
author_facet Ekimoto, Toru
Kokabu, Yuichi
Oroguchi, Tomotaka
Ikeguchi, Mitsunori
author_sort Ekimoto, Toru
collection PubMed
description The combination of molecular dynamics (MD) simulations and small-angle X-ray scattering (SAXS), called the MD-SAXS method, is efficient for investigating protein dynamics. To overcome the time-scale limitation of all-atom MD simulations, coarse-grained (CG) representations are often utilized for biomolecular simulations. In this study, we propose a method to combine CG MD simulations with SAXS, termed the CG-MD-SAXS method. In the CG-MD-SAXS method, the scattering factors of CG particles for proteins and nucleic acids are evaluated using high-resolution structural data in the Protein Data Bank, and the excluded volume and the hydration shell are modeled using two adjustable parameters to incorporate solvent effects. To avoid overfitting, only the two parameters are adjusted for an entire structure ensemble. To verify the developed method, theoretical SAXS profiles for various proteins, DNA/RNA, and a protein-RNA complex are compared with both experimental profiles and theoretical profiles obtained by the all-atom representation. In the present study, we applied the CG-MD-SAXS method to the Swi5-Sfr1 complex and three types of nucleosomes to obtain reliable ensemble models consistent with the experimental SAXS data.
format Online
Article
Text
id pubmed-6976007
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher The Biophysical Society of Japan (BSJ)
record_format MEDLINE/PubMed
spelling pubmed-69760072020-01-24 Combination of coarse-grained molecular dynamics simulations and small-angle X-ray scattering experiments Ekimoto, Toru Kokabu, Yuichi Oroguchi, Tomotaka Ikeguchi, Mitsunori Biophys Physicobiol Regular Article The combination of molecular dynamics (MD) simulations and small-angle X-ray scattering (SAXS), called the MD-SAXS method, is efficient for investigating protein dynamics. To overcome the time-scale limitation of all-atom MD simulations, coarse-grained (CG) representations are often utilized for biomolecular simulations. In this study, we propose a method to combine CG MD simulations with SAXS, termed the CG-MD-SAXS method. In the CG-MD-SAXS method, the scattering factors of CG particles for proteins and nucleic acids are evaluated using high-resolution structural data in the Protein Data Bank, and the excluded volume and the hydration shell are modeled using two adjustable parameters to incorporate solvent effects. To avoid overfitting, only the two parameters are adjusted for an entire structure ensemble. To verify the developed method, theoretical SAXS profiles for various proteins, DNA/RNA, and a protein-RNA complex are compared with both experimental profiles and theoretical profiles obtained by the all-atom representation. In the present study, we applied the CG-MD-SAXS method to the Swi5-Sfr1 complex and three types of nucleosomes to obtain reliable ensemble models consistent with the experimental SAXS data. The Biophysical Society of Japan (BSJ) 2019-11-29 /pmc/articles/PMC6976007/ /pubmed/31984192 http://dx.doi.org/10.2142/biophysico.16.0_377 Text en 2019 © The Biophysical Society of Japan This article is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-sa/4.0/.
spellingShingle Regular Article
Ekimoto, Toru
Kokabu, Yuichi
Oroguchi, Tomotaka
Ikeguchi, Mitsunori
Combination of coarse-grained molecular dynamics simulations and small-angle X-ray scattering experiments
title Combination of coarse-grained molecular dynamics simulations and small-angle X-ray scattering experiments
title_full Combination of coarse-grained molecular dynamics simulations and small-angle X-ray scattering experiments
title_fullStr Combination of coarse-grained molecular dynamics simulations and small-angle X-ray scattering experiments
title_full_unstemmed Combination of coarse-grained molecular dynamics simulations and small-angle X-ray scattering experiments
title_short Combination of coarse-grained molecular dynamics simulations and small-angle X-ray scattering experiments
title_sort combination of coarse-grained molecular dynamics simulations and small-angle x-ray scattering experiments
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976007/
https://www.ncbi.nlm.nih.gov/pubmed/31984192
http://dx.doi.org/10.2142/biophysico.16.0_377
work_keys_str_mv AT ekimototoru combinationofcoarsegrainedmoleculardynamicssimulationsandsmallanglexrayscatteringexperiments
AT kokabuyuichi combinationofcoarsegrainedmoleculardynamicssimulationsandsmallanglexrayscatteringexperiments
AT oroguchitomotaka combinationofcoarsegrainedmoleculardynamicssimulationsandsmallanglexrayscatteringexperiments
AT ikeguchimitsunori combinationofcoarsegrainedmoleculardynamicssimulationsandsmallanglexrayscatteringexperiments