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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.

SUBMITTER: Kontijevskis A 

PROVIDER: S-EPMC1817660 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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A look inside HIV resistance through retroviral protease interaction maps.

Kontijevskis Aleksejs A   Prusis Peteris P   Petrovska Ramona R   Yahorava Sviatlana S   Mutulis Felikss F   Mutule Ilze I   Komorowski Jan J   Wikberg Jarl E S JE  

PLoS computational biology 20070124 3


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  ...[more]

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