Computational identification of novel amino-acid interactions in HIV Gag via correlated evolution

PLoS One. 2012;7(8):e42468. doi: 10.1371/journal.pone.0042468. Epub 2012 Aug 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Amino Acids
  • gag Gene Products, Human Immunodeficiency Virus

Grants and funding

H-GK and JAGB and were supported by a grant from the Deutsche Forschungsgemeinschaft within SPP 1175. OVK was partially supported by an EMBO Long Term Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.