BLEEP?potential of mean force describing protein-ligand interactions: I. Generating potential

✍ Scribed by Mitchell, John B. O.; Laskowski, Roman A.; Alex, Alexander; Thornton, Janet M.

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 239 KB
• Volume: 20
• Category: Article
• ISSN: 0192-8651
• DOI: 10.1002/(sici)1096-987x(199908)20:11<1165::aid-jcc7>3.0.co;2-a

✦ Synopsis

We have developed BLEEP biomolecular ligand energy evaluation .

Ž . protocol , an atomic level potential of mean force PMF describing protein᎐ligand interactions. The pair potentials for BLEEP have been derived from high-resolution X-ray structures of protein᎐ligand complexes in the Ž . Brookhaven Protein Data Bank PDB , with a careful treatment of homology. The use of a broad variety of protein᎐ligand structures in the derivation phase gives BLEEP more general applicability than previous potentials, which have been based on limited classes of complexes, and thus represents a significant step forward. We calculate the distance distributions in protein᎐ligand interactions for all 820 possible pairs that can be chosen from our set of 40 different atom types, including polar hydrogen. We then use a reverse Boltzmann methodology to convert these into energy-like pair potential functions. Two versions of BLEEP are calculated, one including and one excluding interactions between protein and water. The pair potentials are found to have the expected forms; polar and hydrogen bonding interactions show minima at short range, åround 3.0 A, whereas a typical hydrophobic interaction is repulsive at this distance, with values above 4.0 A being preferred.