HIV-1 Protease Dimerization Dynamics Reveals a Transient Druggable Binding Pocket at the Interface.

ABSTRACT: The binding mechanism of HIV-1 protease monomers leading to the catalytically competent dimeric enzyme has been investigated by means of state-of-the-art atomistic simulations. The emerging picture allows a deeper understanding of experimental observations and reveals that water molecules trapped at the interface have an important role in slowing down the kinetics of the association process. Unexpectedly, a cryptic binding pocket is identified at the interface of the complex, corresponding to a partially bound dimer that lacks enzymatic function. The pocket has a transient nature with a lifetime longer than 1 μs, and it displays very favorable druggability features. Docking as well as MM-GBSA free-energy calculations further support the possibility to target the new binding site by means o

SUBMITTER: Pietrucci F 

PROVIDER: S-EPMC4686983 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature