BLEEP?potential of mean force describing protein-ligand interactions: II. Calculation of binding energies and comparison with experimental data

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

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 277 KB
• Volume: 20
• Category: Article
• ISSN: 0192-8651
• DOI: 10.1002/(sici)1096-987x(199908)20:11<1177::aid-jcc8>3.0.co;2-0

✦ Synopsis

We have developed BLEEP biomolecular ligand energy evaluation .

Ž . protocol , an atomic level potential of mean force PMF describing protein᎐ligand interactions. Here, we present four tests designed to assess different attributes of BLEEP. Calculating the energy of a small hydrogen-bonded complex allows us to compare BLEEP's description of this system with a quantum-chemical description. The results suggest that BLEEP gives an adequate description of hydrogen bonding. A study of the relative energies of various Ž . heparin binding geometries for human basic fibroblast growth factor bFGF demonstrates that BLEEP performs excellently in identifying low-energy binding modes from decoy conformations for a given protein᎐ligand complex. We also calculate binding energies for a set of 90 protein᎐ligand complexes, obtaining a correlation coefficient of 0.74 when compared with experiment. This shows that BLEEP can perform well in the difficult area of ranking the interaction energies of diverse complexes. We also study a set of nine serine proteinase᎐inhibitor complexes; BLEEP's good performance here illustrates its ability to determine the