Tandem domain structure determination based on a systematic enumeration of conformations

Abstract Protein structure determination is undergoing a change of perspective due to the larger importance taken in biology by the disordered regions of biomolecules. In such cases, the convergence criterion is more difficult to set up and the size of the conformational space is a obstacle to exhau...

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Autor principal:	Thérèse E. Malliavin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b859c69229b48e990be57a652283d2d
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spelling	oai:doaj.org-article:5b859c69229b48e990be57a652283d2d2021-12-02T15:10:34ZTandem domain structure determination based on a systematic enumeration of conformations10.1038/s41598-021-96370-z2045-2322https://doaj.org/article/5b859c69229b48e990be57a652283d2d2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96370-zhttps://doaj.org/toc/2045-2322Abstract Protein structure determination is undergoing a change of perspective due to the larger importance taken in biology by the disordered regions of biomolecules. In such cases, the convergence criterion is more difficult to set up and the size of the conformational space is a obstacle to exhaustive exploration. A pipeline is proposed here to exhaustively sample protein conformations using backbone angle limits obtained by nuclear magnetic resonance (NMR), and then to determine the populations of conformations. The pipeline is applied to a tandem domain of the protein whirlin. An original approach, derived from a reformulation of the Distance Geometry Problem is used to enumerate the conformations of the linker connecting the two domains. Specifically designed procedure then permit to assemble the domains to the linker conformations and to optimize the tandem domain conformations with respect to two sets of NMR measurements: residual dipolar couplings and paramagnetic resonance enhancements. The relative populations of optimized conformations are finally determined by fitting small angle X-ray scattering (SAXS) data. The most populated conformation of the tandem domain is a semi-closed one, fully closed and more extended conformations being in minority, in agreement with previous observations. The SAXS and NMR data show different influences on the determination of populations.Thérèse E. MalliavinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thérèse E. Malliavin Tandem domain structure determination based on a systematic enumeration of conformations
description	Abstract Protein structure determination is undergoing a change of perspective due to the larger importance taken in biology by the disordered regions of biomolecules. In such cases, the convergence criterion is more difficult to set up and the size of the conformational space is a obstacle to exhaustive exploration. A pipeline is proposed here to exhaustively sample protein conformations using backbone angle limits obtained by nuclear magnetic resonance (NMR), and then to determine the populations of conformations. The pipeline is applied to a tandem domain of the protein whirlin. An original approach, derived from a reformulation of the Distance Geometry Problem is used to enumerate the conformations of the linker connecting the two domains. Specifically designed procedure then permit to assemble the domains to the linker conformations and to optimize the tandem domain conformations with respect to two sets of NMR measurements: residual dipolar couplings and paramagnetic resonance enhancements. The relative populations of optimized conformations are finally determined by fitting small angle X-ray scattering (SAXS) data. The most populated conformation of the tandem domain is a semi-closed one, fully closed and more extended conformations being in minority, in agreement with previous observations. The SAXS and NMR data show different influences on the determination of populations.
format	article
author	Thérèse E. Malliavin
author_facet	Thérèse E. Malliavin
author_sort	Thérèse E. Malliavin
title	Tandem domain structure determination based on a systematic enumeration of conformations
title_short	Tandem domain structure determination based on a systematic enumeration of conformations
title_full	Tandem domain structure determination based on a systematic enumeration of conformations
title_fullStr	Tandem domain structure determination based on a systematic enumeration of conformations
title_full_unstemmed	Tandem domain structure determination based on a systematic enumeration of conformations
title_sort	tandem domain structure determination based on a systematic enumeration of conformations
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5b859c69229b48e990be57a652283d2d
work_keys_str_mv	AT thereseemalliavin tandemdomainstructuredeterminationbasedonasystematicenumerationofconformations
_version_	1718387690749034496

Tandem domain structure determination based on a systematic enumeration of conformations

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