SHEF: a vHTS geometrical filter using coefficients of spherical harmonic molecular surfaces

Abstract

SHEF (spherical harmonic coefficient filter), a geometrical matching procedure constituting a preliminary step in the virtual high throughput screening of large databases of small drug-like molecules, is demonstrated. This filter uses a description of both the binding site of the target and the ligand surfaces using spherical harmonic polynomial expansions. Using this representation, which is based on limited sets of spherical harmonic coefficients, considerably reduces the complexity of surface complementarity calculation. As a first test, 188 known protein-ligand complexes were used, and the results of docking the abstracted ligands into the bare proteins using SHEF were compared to the original X-ray structures. The ability of SHEF to retrieve known ligands "hidden" in a virtual library of 1,000 randomly selected drug-like compounds is also demonstrated.