10.1021/ct800152d.s001
Adrian P. Wiley
Adrian P.
Wiley
Sarah L. Williams
Sarah L.
Williams
Jonathan W. Essex
Jonathan W.
Essex
Conformational Motions of HIV-1 Protease Identified Using Reversible Digitally Filtered Molecular Dynamics
American Chemical Society
2009
Reversible Digitally
protease
AIDS
Molecular
protein flaps
HIV
RDFMD
MD
coli dihydrofolate reductase
NMR
simulation
2009-04-14 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Conformational_Motions_of_HIV_1_Protease_Identified_Using_Reversible_Digitally_Filtered_Molecular_Dynamics/2864437
HIV-1 protease performs a vital step in the propagation of the HIV virus and is therefore an important drug target in the treatment of AIDS. It consists of a homodimer, with access to the active site limited by two protein flaps. NMR studies have identified two time scales of motions that occur in these flaps, and it is thought that the slower of these is responsible for a conformational change that makes the protein ligand-accessible. This motion occurs on a time scale outside that achievable using traditional molecular dynamics simulations. Reversible Digitally Filtered Molecular Dynamics (RDFMD) is a method that amplifies low frequency motions associated with conformational change and has recently been applied to, among others, <i>E. coli</i> dihydrofolate reductase, inducing a conformational change between known crystal structures. In this paper, the conformational motions of HIV-1 protease produced during MD and RDFMD simulations are presented, including movement between the known semiopen and closed conformations, and the opening and closing of the protein flaps.