A look inside HIV resistance through retroviral protease interaction maps
2007 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 3, no 3, 424-435 p.Article in journal (Refereed) Published
Retroviruses affect a large number of species, from fish and birds to mammals and humans, with global socioeconomic negative impacts. Here the authors report and experimentally validate a novel approach for the analysis of the molecular networks that are involved in the recognition of substrates by retroviral proteases. Using multivariate analysis of the sequence-based physiochemical descriptions of 61 retroviral proteases comprising wild-type proteases, natural mutants, and drug-resistant forms of proteases from nine different viral species in relation to their ability to cleave 299 substrates, the authors mapped the physicochemical properties and cross-dependencies of the amino acids of the proteases and their substrates, which revealed a complex molecular interaction network of substrate recognition and cleavage. The approach allowed a detailed analysis of the molecular-chemical mechanisms involved in substrate cleavage by retroviral proteases.
Place, publisher, year, edition, pages
2007. Vol. 3, no 3, 424-435 p.
Proteochemometrics, HIV, resistance, drug discovery, PLS, protein-ligand interactions
IdentifiersURN: urn:nbn:se:uu:diva-97333DOI: 10.1371/journal.pcbi.0030048ISI: 000246191000009PubMedID: 17352531OAI: oai:DiVA.org:uu-97333DiVA: diva2:172220