title: Impact of M36I polymorphism on the interaction of HIV-1 protease with its substrates: insights from molecular dynamics.
abstract: BACKGROUND
  Over the last decades, a vast structural knowledge has been gathered on the HIV-1 protease (PR). Noticeably, most of the studies focused the B-subtype, which has the highest prevalence in developed countries. Accordingly, currently available anti-HIV drugs target this subtype, with considerable benefits for the corresponding patients.
  
  
  RESULTS
  Herein, we used molecular dynamics simulations to investigate the role of this polymorphism on the interaction of PR with six of its natural cleavage-sites substrates.
  
  
  CONCLUSIONS
  With multiple approaches and analyses we identified structural and dynamical determinants associated with the changes found in the binding affinity of the M36I variant. This mutation influences the flexibility of both PR and its complexed substrate. The observed impact of M36I, suggest that combination with other non-B subtype polymorphisms, could lead to major effects on the interaction with the 12 known cleavage sites, which should impact the virion maturation.
authors.forename: Mauricio G S
authors.initials: MG
authors.lastname: Costa
authors.forename: Técio G
authors.initials: TG
authors.lastname: Benetti-Barbosa
authors.forename: Nathan
authors.initials: N
authors.lastname: Desdouits
authors.forename: Arnaud
authors.initials: A
authors.lastname: Blondel
authors.forename: Paulo M
authors.initials: PM
authors.lastname: Bisch
authors.forename: Pedro G
authors.initials: PG
authors.lastname: Pascutti
authors.forename: Paulo R
authors.initials: PR
authors.lastname: Batista
mesh_terms: D001665:Binding Sites / Q000235:genetics; D003198:Computer Simulation; D016333:HIV Protease / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D056004:Molecular Dynamics Simulation; D011110:Polymorphism, Genetic; D011485:Protein Binding / Q000235:genetics; D013379:Substrate Specificity / Q000235:genetics; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D017320:HIV Protease Inhibitors; D008024:Ligands; D014764:Viral Proteins; D016333:HIV Protease