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Free keywords:
Amino Acid Sequence
Amino Acids/*metabolism
Computational Biology/*methods
*Evolution, Molecular
HIV/genetics/pathogenicity
Models, Molecular
Molecular Sequence Data
gag Gene Products, Human Immunodeficiency Virus/*chemistry/*genetics
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.