Rapid sampling of molecular motions with prior information constraints.

Proteins are active, flexible machines that perform a range of different functions. Innovative experimental approaches may now provide limited partial information about conformational changes along motion pathways of proteins. There is therefore a need for computational approaches that can efficient...

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Autores principales:	Barak Raveh, Angela Enosh, Ora Schueler-Furman, Dan Halperin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/32573e12464a40a8a863bffe9bd70563
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spelling	oai:doaj.org-article:32573e12464a40a8a863bffe9bd705632021-11-25T05:41:50ZRapid sampling of molecular motions with prior information constraints.1553-734X1553-735810.1371/journal.pcbi.1000295https://doaj.org/article/32573e12464a40a8a863bffe9bd705632009-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19247429/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Proteins are active, flexible machines that perform a range of different functions. Innovative experimental approaches may now provide limited partial information about conformational changes along motion pathways of proteins. There is therefore a need for computational approaches that can efficiently incorporate prior information into motion prediction schemes. In this paper, we present PathRover, a general setup designed for the integration of prior information into the motion planning algorithm of rapidly exploring random trees (RRT). Each suggested motion pathway comprises a sequence of low-energy clash-free conformations that satisfy an arbitrary number of prior information constraints. These constraints can be derived from experimental data or from expert intuition about the motion. The incorporation of prior information is very straightforward and significantly narrows down the vast search in the typically high-dimensional conformational space, leading to dramatic reduction in running time. To allow the use of state-of-the-art energy functions and conformational sampling, we have integrated this framework into Rosetta, an accurate protocol for diverse types of structural modeling. The suggested framework can serve as an effective complementary tool for molecular dynamics, Normal Mode Analysis, and other prevalent techniques for predicting motion in proteins. We applied our framework to three different model systems. We show that a limited set of experimentally motivated constraints may effectively bias the simulations toward diverse predicates in an outright fashion, from distance constraints to enforcement of loop closure. In particular, our analysis sheds light on mechanisms of protein domain swapping and on the role of different residues in the motion.Barak RavehAngela EnoshOra Schueler-FurmanDan HalperinPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 5, Iss 2, p e1000295 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Barak Raveh Angela Enosh Ora Schueler-Furman Dan Halperin Rapid sampling of molecular motions with prior information constraints.
description	Proteins are active, flexible machines that perform a range of different functions. Innovative experimental approaches may now provide limited partial information about conformational changes along motion pathways of proteins. There is therefore a need for computational approaches that can efficiently incorporate prior information into motion prediction schemes. In this paper, we present PathRover, a general setup designed for the integration of prior information into the motion planning algorithm of rapidly exploring random trees (RRT). Each suggested motion pathway comprises a sequence of low-energy clash-free conformations that satisfy an arbitrary number of prior information constraints. These constraints can be derived from experimental data or from expert intuition about the motion. The incorporation of prior information is very straightforward and significantly narrows down the vast search in the typically high-dimensional conformational space, leading to dramatic reduction in running time. To allow the use of state-of-the-art energy functions and conformational sampling, we have integrated this framework into Rosetta, an accurate protocol for diverse types of structural modeling. The suggested framework can serve as an effective complementary tool for molecular dynamics, Normal Mode Analysis, and other prevalent techniques for predicting motion in proteins. We applied our framework to three different model systems. We show that a limited set of experimentally motivated constraints may effectively bias the simulations toward diverse predicates in an outright fashion, from distance constraints to enforcement of loop closure. In particular, our analysis sheds light on mechanisms of protein domain swapping and on the role of different residues in the motion.
format	article
author	Barak Raveh Angela Enosh Ora Schueler-Furman Dan Halperin
author_facet	Barak Raveh Angela Enosh Ora Schueler-Furman Dan Halperin
author_sort	Barak Raveh
title	Rapid sampling of molecular motions with prior information constraints.
title_short	Rapid sampling of molecular motions with prior information constraints.
title_full	Rapid sampling of molecular motions with prior information constraints.
title_fullStr	Rapid sampling of molecular motions with prior information constraints.
title_full_unstemmed	Rapid sampling of molecular motions with prior information constraints.
title_sort	rapid sampling of molecular motions with prior information constraints.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/32573e12464a40a8a863bffe9bd70563
work_keys_str_mv	AT barakraveh rapidsamplingofmolecularmotionswithpriorinformationconstraints AT angelaenosh rapidsamplingofmolecularmotionswithpriorinformationconstraints AT oraschuelerfurman rapidsamplingofmolecularmotionswithpriorinformationconstraints AT danhalperin rapidsamplingofmolecularmotionswithpriorinformationconstraints
_version_	1718414510157463552

Rapid sampling of molecular motions with prior information constraints.

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