Ab Initio potential grid based docking: From High Performance Computing to In Silico Screening

We present a new method for the generation of potential grids for protein-ligand docking. The potential of the docking target structure is obtained directly from the electron density derived through an ab initio computation. A large subregion was selected to allow the full ab initio treatment of a the Isocitrate Lyase enzyme. The electrostatic potential is tested by docking a small charged molecule (succinate) into the binding site. The ab initio grid yields a superior result by producing the best binding orientation and position, and by recognizing it as the best. In contrast the same docking procedure, but using a classical point-charge based potential, produces a number of additional incorrect binding poses, and does not recognize the correct pose as the best solution.