Modified AutoDock for accurate docking of protein kinase inhibitors.

摘要: Protein kinases are an important class of enzymes controlling virtually all cellular signaling pathways. Consequently, selective inhibitors protein have attracted significant interest as potential new drugs for many diseases. Computational methods, including molecular docking, increasingly been used in the inhibitor design process [1]. We considered several docking packages order to strengthen our kinase work with computational capabilities. In experience, AutoDock offered a reasonable combination accuracy and speed, opposed methods that specialize either fast database searches or detailed computationally intensive calculations. However, did not perform well cases where extensive hydrophobic contacts were involved, such SB203580 its target p38. Another shortcoming was hydrogen bonding energy function, which underestimated attraction component and, thus, allow sufficiently accurate modeling key bonds kinase-inhibitor complexes. modified parameter set model bonds, increased appeared be generally applicable pairs without customization. Binding largely sites, active site p38, significantly improved by introducing correction factor selectively affecting only carbon grids, providing effective, although approximate, treatment solvation.