Mechanism of action of cyclophilin a explored by metadynamics simulations.

Leone, Vanessa; Lattanzi, Gianluca; Molteni, Carla; Carloni, Paolo · PLoS Comput Biol · 2009

basic_science · Level V

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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.

Medical subject headings