title: Mechanism of action of cyclophilin a explored by metadynamics simulations.
abstract: Trans/cis prolyl isomerisation is involved in several biological processes, including the development of numerous diseases. In the HIV-1 capsid protein (CA), such a process takes place in the uncoating and recruitment of the virion and is catalyzed by cyclophilin A (CypA). Here, we use metadynamics simulations to investigate the isomerization of CA's model substrate HAGPIA in water and in its target protein CypA. Our results allow us to propose a novel mechanistic hypothesis, which is finally consistent with all of the available molecular biology data.
authors.affiliation: International School for Advanced Studies (SISSA), Trieste, Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Leone
authors.forename: Gianluca
authors.initials: G
authors.lastname: Lattanzi
authors.forename: Carla
authors.initials: C
authors.lastname: Molteni
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
mesh_terms: D001665:Binding Sites; D036022:Capsid Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D003198:Computer Simulation; D021984:Cyclophilin A / Q000737:chemistry*; D004789:Enzyme Activation; D015497:HIV-1 / Q000737:chemistry*; D007536:Isomerism; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D014867:Water / Q000737:chemistry*
chemical_list: D036022:Capsid Proteins; D014867:Water; D021984:Cyclophilin A