Creating artificial binding pocket boundaries to improve the efficiency of flexible ligand docking

Traditionally, algorithms for binding site characterization or identification focus on the problem of identifying atoms within a macromolecule that might be responsible for ligand binding. In this manuscript, we focus on the binding pocket problem from a different perspective as a challenge of calculating an artificial binding pocket boundary that is sufficient to isolate binding pocket volume. The approach involves the calculation of a macromolecule encapsulating surface (MES) that separates binding pocket volume from outside space. We show that the MES can be used to increase the efficiency of flexible docking as implemented in AutoDock 3.0. The most significant improvement in docking efficiency is seen when the entire protein is searched and results show additional support for the use of AutoDock, in and of itself, as a feasible tool for binding-site identification for cases in which a protein ligand is known.