Molecular simulations using spherical harmonics

Abstract

Computer-aided drug design is to develop a chemical that binds to a target macromolecule known to play a key role in a disease state. In recognition of ligands by their protein receptors, molecular surfaces are often used because they represent the interacting part of molecules and they should reflex the complementarity between ligand and receptor. However, assessing the surface complementarity by searching all relative position of two surfaces is often computationally expensive. The complementarity of lobe-hole is very important in protein-ligand interactions. Spherical harmonic models based on expansions of spherical harmonic functions were used as a fingerprint to approximate the binding cavity and the ligand, respectively. This defines a new way to identify the complementarity between lobes and holes. The advantage of this method is that two spherical harmonic surfaces to be compared can be defined separately. This method can be used as a filter to eliminate candidates among a large number of conformations, and it will speed up the docking procedure. Therefore, it is possible to select complementary ligands or complementary conformations of a ligand and the macromolecules, by comparing their fingerprints previously stored in a database.