Biopolymers and cell. 2002; 18 (2): 117 - 123

Conformational changes in HIV-1 protease: molecular dynamic simulation study in picoseond and nanosecond timescales

D. B. Kovalsky, A. I. Kornelyuk

HIV-1 protease is one of the most important drug design targets in AIDS therapy. A two fi-strands covering active site play central role in its function. To permit substrate entrance into active site they must open. Despite great knowledge of HI V-1 protease structure a flap opening mechanism is still unclear. Here we perform molecular dynamic simulation of HIV-1 protease in vacuum and in solution, in picosecond and nanosecond timescales. Structural «dynamic» binding pocket formation is observed like as in vacuum simulation as in solution. The most pan of residues forming the binding pocket are hydrophobic. These residues are: Val32, Lys45, Ile47, Gly48, Gly49, IleSO, GlySl, Gly52, Ile54, VaL56, Leu.76, Gly78, Pro79, ThrSO, ProSl. In spite of great its flexibility it remains well-defined during the the simulation. We assume that the pocket could be used in drug design.