title: Computational identification of novel amino-acid interactions in HIV Gag via correlated evolution.
abstract: Pairs of amino acid positions that evolve in a correlated manner are proposed to play important roles in protein structure or function. Methods to detect them might fare better with families for which sequences of thousands of closely related homologs are available than families with only a few distant relatives. We applied co-evolution analysis to thousands of sequences of HIV Gag, finding that the most significantly co-evolving positions are proximal in the quaternary structures of the viral capsid. A reduction in infectivity caused by mutating one member of a significant pair could be rescued by a compensatory mutation of the other.
authors.affiliation: CellNetworks, Bioquant, University of Heidelberg, Heidelberg, Germany.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Kalinina
authors.forename: Heike
authors.initials: H
authors.lastname: Oberwinkler
authors.forename: Bärbel
authors.initials: B
authors.lastname: Glass
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Kräusslich
authors.forename: Robert B
authors.initials: RB
authors.lastname: Russell
authors.forename: John A G
authors.initials: JA
authors.lastname: Briggs
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods*; D019143:Evolution, Molecular; D006678:HIV / Q000235:genetics / Q000472:pathogenicity; D008958:Models, Molecular; D008969:Molecular Sequence Data; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics*
chemical_list: D000596:Amino Acids; D054301:gag Gene Products, Human Immunodeficiency Virus