Toward high throughput 3D virtual screening using spherical harmonic surface representations.

Searching chemical databases for possible drug leads is often one of the main activities conducted during the early stages of a drug development project. This article shows that spherical harmonic molecular shape representations provide a powerful way to search and cluster small-molecule databases rapidly and accurately. Our clustering results show that chemically meaningful clusters may be obtained using only low order spherical harmonic expansions. Our database search results show that using low order spherical harmonic shape-based correlation techniques could provide a practical and efficient way to search very large 3D molecular databases, hence leading to a useful new approach for high throughput 3D virtual screening. The approach described is currently being extended to allow the rapid search and comparison of arbitrary combinations of molecular surface properties.