A hybrid method of molecular dynamics and harmonic dynamics for docking of flexible ligand to flexible receptor.
We have developed a new docking method to consider receptor flexibility, a hybrid method of molecular dynamics and harmonic dynamics. The global motions of the whole receptor were approximately introduced into those of the receptor in the docking simulation as harmonic dynamics. On the other hand, the local flexibility of the side chains was also considered by conventional molecular dynamics. We confirmed that this new method can reproduce the fluctuations of the whole receptor by making a comparison of the directions and amplitudes of the global fluctuations. Then this method was applied to the docking of HIV-1 protease and its ligand. As a result, we observed a docking process where the ligand enters into the binding pocket well, which implies that this method is effective enough to reproduce a molecular complex formation.
Japan Biological Information Research Center, Japan Biological Informatics Consortium, Aomi 2-41-6, Koto-ku, Tokyo 135-0064, Japan. tatsumi@jbirc.aist.go.jp
Rie
R
Tatsumi
Yoshifumi
Y
Fukunishi
Haruki
H
Nakamura
D000465:Algorithms; D002627:Chemistry, Physical / Q000379:methods*; D003198:Computer Simulation; D016333:HIV Protease / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D013816:Thermodynamics
D008024:Ligands; D016333:HIV Protease