Journal of Computer-Aided Molecular Design

, Volume 14, Issue 4, pp 383–401 | Cite as

Fast prediction and visualization of protein binding pockets with PASS

  • G. Patrick BradyJr
  • Pieter F.W. Stouten
Article

Abstract

PASS (Putative Active Sites with Spheres) is a simple computational tool that uses geometry to characterize regions of buried volume in proteins and to identify positions likely to represent binding sites based upon the size, shape, and burial extent of these volumes. Its utility as a predictive tool for binding site identification is tested by predicting known binding sites of proteins in the PDB using both complexed macromolecules and their corresponding 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 (∼30 kDa) in under 20 s, which makes it suitable for interactive molecular modeling, protein database analysis, and aggressive virtual screening efforts. As a modeling tool, PASS (i) rapidly identifies favorable regions of the protein surface, (ii) simplifies visualization of residues modulating binding in these regions, and (iii) provides a means of directly visualizing buried volume, which is often inferred indirectly from curvature in a surface representation. PASS 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®, InsightII®, MOE®, Quanta®, RasMol®, and Sybyl®. PASS is freely available to all.

binding site buried volume cavity detection molecular modeling protein active site 

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Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • G. Patrick BradyJr
    • 1
  • Pieter F.W. Stouten
    • 1
  1. 1.Experimental Station E500DuPont Pharmaceuticals CompanyWilmingtonU.S.A.

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