Prediction of stability upon point mutation in the context of the folding nucleus

dc.contributor.author	Lonquety, M	en
dc.contributor.author	Chomilier, J	en
dc.contributor.author	Papandreou, N	en
dc.contributor.author	Lacroix, Z	en
dc.date.accessioned	2014-06-06T06:50:39Z
dc.date.available	2014-06-06T06:50:39Z
dc.date.issued	2010	en
dc.identifier.issn	15362310	en
dc.identifier.uri	http://dx.doi.org/10.1089/omi.2009.0022	en
dc.identifier.uri	http://62.217.125.90/xmlui/handle/123456789/5103
dc.subject.other	ab initio calculation	en
dc.subject.other	algorithm	en
dc.subject.other	article	en
dc.subject.other	computer simulation	en
dc.subject.other	intermethod comparison	en
dc.subject.other	methodology	en
dc.subject.other	Monte Carlo method	en
dc.subject.other	most interacting residue algorithm	en
dc.subject.other	point mutation	en
dc.subject.other	position effect	en
dc.subject.other	priority journal	en
dc.subject.other	protein analysis	en
dc.subject.other	protein database	en
dc.subject.other	protein folding	en
dc.subject.other	protein stability	en
dc.subject.other	protein structure	en
dc.subject.other	protein tertiary structure	en
dc.subject.other	structure analysis	en
dc.subject.other	tightened end fragment	en
dc.subject.other	Algorithms	en
dc.subject.other	Avian Sarcoma Viruses	en
dc.subject.other	Integrases	en
dc.subject.other	Monte Carlo Method	en
dc.subject.other	Point Mutation	en
dc.subject.other	Protein Folding	en
dc.subject.other	Protein Stability	en
dc.subject.other	Proteins	en
dc.title	Prediction of stability upon point mutation in the context of the folding nucleus	en
heal.type	journalArticle	en
heal.identifier.primary	10.1089/omi.2009.0022	en
heal.publicationDate	2010	en
heal.abstract	Proteins come in all shapes and sizes. Although it is possible to predict with reasonable success their structure from their sequence, the process of folding a chain of amino acids into its tertiary structure remains partially understood. This article addresses several characteristics pertaining to protein folding. The development of the Most Interacting Residues (MIR) algorithm, which dynamically simulates the early folding events, permits a reasonable ab initio prediction of the deeply buried critical residues involved in the formation of the protein core. The analysis of MIR positions with respect to protein 3D topology, in particular, to fragments called Tightened End Fragments (TEF) that might be good candidate for autonomous folding units, suggests that they are also essential for defining core stability. To validate this hypothesis, this study measures the sensitivity of MIR residues to point mutations. It is performed on a set of 385 proteins from a database that contains stability data calculated with five different algorithms. Tools have been developed to help the analysis and a consensus of the five methods is proposed. It results that positions predicted both as a MIR and a minimum of stability for the consensus are good candidates for the folding nucleus, and consequently their mutations may be hazardous. © 2010, Mary Ann Liebert, Inc.	en
heal.journalName	OMICS A Journal of Integrative Biology	en
dc.identifier.issue	2	en
dc.identifier.volume	14	en
dc.identifier.doi	10.1089/omi.2009.0022	en
dc.identifier.spage	151	en
dc.identifier.epage	156	en