A coarse grained model for the dynamics of flap opening in HIV-1 protease

A coarse grained model for proteins is developed and applied to HIV-1 protease. Molecular dynamics simulations on the μsec timescale and the use of a flexible force field allow study of the opening of the 'flaps' protecting the active site. The opening mechanism reveals peculiar features that might be involved in the substrate capture. An allosteric inhibition effect is demonstrated in specific regions of the protein. This study indicates alternative conformations and target sites to be used as basis for the design of novel inhibitor drugs.