A molecular dynamics study of Cyclophilin A free and in complex with the Ala-Pro dipeptide.

Six different molecular dynamics simulations of Cyclophilin A, three with the protein free in water and three with the Ala-Pro dipeptide bound to the protein, have been performed, and analysed with respect to structure and hydration of the active site. The water structure in the binding pocket of the free Cyclophilin A was found to mimic the experimentally obtained binding cis conformation of the dipeptide. Cyclophilin A is a peptidyl-prolyl cis-trans isomerase (PPIase), but the mechanism of the cis/trans isomerization is not exactly clear. This study was performed to understand better the binding between dipeptide and Cyclophilin A, but also two previously proposed isomerization mechanisms are discussed.