Modeling Conformationally Flexible Proteins With X-ray Scattering and Molecular Simulations

Proteins and protein complexes with high conformational flexibility participate in a wide range of biological processes. These processes include genome maintenance, gene expression, signal transduction, cell cycle regulation, and many others. Gaining a structural understanding of conformationally fl...

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Detalles Bibliográficos
Autores principales: Powers, Kyle T., Gildenberg, Melissa S., Washington, M. Todd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Research Network of Computational and Structural Biotechnology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495069/
https://www.ncbi.nlm.nih.gov/pubmed/31073392
http://dx.doi.org/10.1016/j.csbj.2019.04.011
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author Powers, Kyle T.
Gildenberg, Melissa S.
Washington, M. Todd
author_facet Powers, Kyle T.
Gildenberg, Melissa S.
Washington, M. Todd
author_sort Powers, Kyle T.
collection PubMed
description Proteins and protein complexes with high conformational flexibility participate in a wide range of biological processes. These processes include genome maintenance, gene expression, signal transduction, cell cycle regulation, and many others. Gaining a structural understanding of conformationally flexible proteins and protein complexes is arguably the greatest problem facing structural biologists today. Over the last decade, some progress has been made toward understanding the conformational flexibility of such systems using hybrid approaches. One particularly fruitful strategy has been the combination of small-angle X-ray scattering (SAXS) and molecular simulations. In this article, we provide a brief overview of SAXS and molecular simulations and then discuss two general approaches for combining SAXS data and molecular simulations: minimal ensemble approaches and full ensemble approaches. In minimal ensemble approaches, one selects a minimal ensemble of structures from the simulations that best fit the SAXS data. In full ensemble approaches, one validates a full ensemble of structures from the simulations using SAXS data. We argue that full ensemble models are more realistic than minimal ensemble searches models and that full ensemble approaches should be used wherever possible.
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spelling pubmed-64950692019-05-09 Modeling Conformationally Flexible Proteins With X-ray Scattering and Molecular Simulations Powers, Kyle T. Gildenberg, Melissa S. Washington, M. Todd Comput Struct Biotechnol J Review Article Proteins and protein complexes with high conformational flexibility participate in a wide range of biological processes. These processes include genome maintenance, gene expression, signal transduction, cell cycle regulation, and many others. Gaining a structural understanding of conformationally flexible proteins and protein complexes is arguably the greatest problem facing structural biologists today. Over the last decade, some progress has been made toward understanding the conformational flexibility of such systems using hybrid approaches. One particularly fruitful strategy has been the combination of small-angle X-ray scattering (SAXS) and molecular simulations. In this article, we provide a brief overview of SAXS and molecular simulations and then discuss two general approaches for combining SAXS data and molecular simulations: minimal ensemble approaches and full ensemble approaches. In minimal ensemble approaches, one selects a minimal ensemble of structures from the simulations that best fit the SAXS data. In full ensemble approaches, one validates a full ensemble of structures from the simulations using SAXS data. We argue that full ensemble models are more realistic than minimal ensemble searches models and that full ensemble approaches should be used wherever possible. Research Network of Computational and Structural Biotechnology 2019-04-22 /pmc/articles/PMC6495069/ /pubmed/31073392 http://dx.doi.org/10.1016/j.csbj.2019.04.011 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review Article
Powers, Kyle T.
Gildenberg, Melissa S.
Washington, M. Todd
Modeling Conformationally Flexible Proteins With X-ray Scattering and Molecular Simulations
title Modeling Conformationally Flexible Proteins With X-ray Scattering and Molecular Simulations
title_full Modeling Conformationally Flexible Proteins With X-ray Scattering and Molecular Simulations
title_fullStr Modeling Conformationally Flexible Proteins With X-ray Scattering and Molecular Simulations
title_full_unstemmed Modeling Conformationally Flexible Proteins With X-ray Scattering and Molecular Simulations
title_short Modeling Conformationally Flexible Proteins With X-ray Scattering and Molecular Simulations
title_sort modeling conformationally flexible proteins with x-ray scattering and molecular simulations
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495069/
https://www.ncbi.nlm.nih.gov/pubmed/31073392
http://dx.doi.org/10.1016/j.csbj.2019.04.011
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