A new, fast, and easy-to-implement method, van der Waals-fast Fourier trans
form (vdW-FFT), for locating possible binding sites on the surface of a pro
tein was developed and tested on a set of 15 different enzyme-ligand comple
xes. The method scans the whole protein surface and possible ligand orienta
tions in order to find the best geometrical match, which corresponds to the
minimum of the modified vdW energy. Two different grids, fine and coarse,
and two sets of MM parameters, from the OPLS and AMBER-94 force fields, wer
e used. The method has been shown to work accurately on the fine grid. On t
he coarse grid, the vdW-FFT method failed only on two complexes. The C prog
ram implementing the method and test set of proteins is available free on o
ur web site: http://biocomp.anu.edu.au/ similar to aab. (C) 1999 John Wiley
& Sons, Inc.