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.
Mechanism of action of cyclophilin a explored by metadynamics simulations / Leone, Vanessa; Lattanzi, Gianluca; Molteni, Carla; Carloni, Paolo. - In: PLOS COMPUTATIONAL BIOLOGY. - ISSN 1553-734X. - 5:3(2009), pp. e1000309.1-e1000309.15. [10.1371/journal.pcbi.1000309]
Mechanism of action of cyclophilin a explored by metadynamics simulations
Lattanzi, Gianluca;
2009-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione
