Mechanism of action of cyclophilin a explored by metadynamics simulations.
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.
Leone
Vanessa
V
International School for Advanced Studies (SISSA), Trieste, Italy.
Lattanzi
Gianluca
G
Molteni
Carla
C
Carloni
Paolo
P
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*
D036022:Capsid Proteins; D014867:Water; D021984:Cyclophilin A