Fast prediction and visualization of protein binding pockets with PASS

PASS (Putative Active Sites with Spheres) is a simple computational tool th at uses geometry to characterize regions of buried volume in proteins and t o identify positions likely to represent binding sites based upon the size, shape, and burial extent of these volumes. Its utility as a predictive too l for binding site identification is tested by predicting known binding sit es of proteins in the PDB using both complexed macromolecules and their cor responding apo-protein structures. The results indicate that PASS can serve as a front-end to fast docking. The main utility of PASS lies in the fact that it can analyze a moderate-size protein (similar to 30 kDa) in under 20 s, which makes it suitable for interactive molecular modeling, protein dat abase analysis, and aggressive virtual screening efforts. As a modeling too l, PASS (i) rapidly identifies favorable regions of the protein surface, (i i) simplifies visualization of residues modulating binding in these regions , and (iii) provides a means of directly visualizing buried volume, which i s often inferred indirectly from curvature in a surface representation. PAS S produces output in the form of standard PDB files, which are suitable for any modeling package, and provides script files to simplify visualization in Cerius2(R), InsightII(R), MOE(R), Quanta(R), RasMol(R), and Sybyl(R). PA SS is freely available to all.