Molecular Simulations using Spherical Harmonics
摘要
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 in-teracting part of molecules and they should reflex the comple-mentarity between ligand and receptor. However, assessing the surface complementarity by searching all relative position of two surfaces is often computationally expensive. The comple-mentarity of lobe-hole is very important in protein-ligand inter-actions. Spherical harmonic models based on expansions of spherical harmonic functions were used as a f'mgerprint to ap-proximate 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 sep-arately. This method can be used as a filter to eliminate candi-dates 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.