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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1783415328729989120 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6495069 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Research Network of Computational and Structural Biotechnology |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT powerskylet modelingconformationallyflexibleproteinswithxrayscatteringandmolecularsimulations AT gildenbergmelissas modelingconformationallyflexibleproteinswithxrayscatteringandmolecularsimulations AT washingtonmtodd modelingconformationallyflexibleproteinswithxrayscatteringandmolecularsimulations |