Blind docking method combining search of low-resolution binding sites with ligand pose refinement by molecular dynamics-based global optimization.
This study describes the development of a new blind hierarchical docking method, bhDock, its implementation, and accuracy assessment. The bhDock method uses two-step algorithm. First, a comprehensive set of low-resolution binding sites is determined by analyzing entire protein surface and ranked by a simple score function. Second, ligand position is determined via a molecular dynamics-based method of global optimization starting from a small set of high ranked low-resolution binding sites. The refinement of the ligand binding pose starts from uniformly distributed multiple initial ligand orientations and uses simulated annealing molecular dynamics coupled with guided force-field deformation of protein-ligand interactions to find the global minimum. Assessment of the bhDock method on the set of 37 protein-ligand complexes has shown the success rate of predictions of 78%, which is better than the rate reported for the most cited docking methods, such as AutoDock, DOCK, GOLD, and FlexX, on the same set of complexes.
Vorobjev
Yury N
YN
Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Science, Novosibirsk, Russia. ynvorob@niboch.nsc.ru
D001665:Binding Sites; D008024:Ligands; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
D008024:Ligands; D011506:Proteins