The influence of macromolecular crowding on HIV-1 protease internal dynamics.
High macromolecular concentrations, or crowded conditions, have been shown to affect a wide variety of molecular processes, including diffusion, association and dissociation, and protein folding and stability. Here, we model the effect of macromolecular crowding on the internal dynamics of a protein, HIV-1 protease, using Brownian dynamics simulations. HIV-1 protease possesses a pair of flaps which are postulated to open in the early stages of its catalytic mechanism. Compared to low concentrations, close-packed concentrations of repulsive crowding agents are found to significantly reduce the fraction of time that the protease flaps are open. Macromolecular crowding is likely to have a major effect on in vivo enzyme activity, and may play an important regulatory role in the viral life cycle.
Minh
David D L
DD
Department of Chemistry & Biochemistry, Center for Theoretical Biological Physics, University of California at San Diego, La Jolla, California 92093-0365, USA. dminh@mccammon.ucsd.edu
Chang
Chia-en
CE
Trylska
Joanna
J
Tozzini
Valentina
V
McCammon
J Andrew
JA