title: A look inside HIV resistance through retroviral protease interaction maps.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Aleksejs
authors.initials: A
authors.lastname: Kontijevskis
authors.forename: Peteris
authors.initials: P
authors.lastname: Prusis
authors.forename: Ramona
authors.initials: R
authors.lastname: Petrovska
authors.forename: Sviatlana
authors.initials: S
authors.lastname: Yahorava
authors.forename: Felikss
authors.initials: F
authors.lastname: Mutulis
authors.forename: Ilze
authors.initials: I
authors.lastname: Mutule
authors.forename: Jan
authors.initials: J
authors.lastname: Komorowski
authors.forename: Jarl E S
authors.initials: JE
authors.lastname: Wikberg
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D024882:Drug Resistance, Viral / Q000502:physiology*; D015497:HIV-1 / Q000201:enzymology; D008954:Models, Biological; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods; D012190:Retroviridae / Q000201:enzymology*; D012191:Retroviridae Proteins / Q000737:chemistry*; D020539:Sequence Analysis, Protein / Q000379:methods*; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D012191:Retroviridae Proteins; D010447:Peptide Hydrolases