Fourier-filtered van der Waals contact surfaces: accurate ligand shapes from protein structures

We describe an improved method for determining the shapes and positions of ligand binding sites on proteins by calculating difference contact surfaces of proteins. We report that such calculations may be carried out efficiently by using the principle of the convolution functional operation. Key to this method are (i) use of contact surfaces rather than accessible surfaces, (ii) use of Fourier filtering to smooth binding site features for which the surface features fluctuate too sporadically to correspond with the shape of a true ligand, and (iii) use of Fourier filtering to obtain a simplified intermediate surface to distinguish between non-contiguous adjacent binding sites. This method for determining the shape and location of substrate binding sites has successfully located a number of experimentally observed substrate binding sites for several different ligands bound to several different proteins and it predicts consistent shapes and positions for previously unobserved substrate binding sites. The shapes of the sites calculated by this algorithm are closer to the shapes of the actual ligands than are shapes of similar sites calculated by other, presently available software. We expect that this method shall be of general utility for predicting protein-ligand interactions.