Premium
B LEEP —potential of mean force describing protein–ligand interactions: II. Calculation of binding energies and comparison with experimental data
Author(s) -
Mitchell John B. O.,
Laskowski Roman A.,
Alex Alexander,
Forster Mark J.,
Thornton Janet M.
Publication year - 1999
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/(sici)1096-987x(199908)20:11<1177::aid-jcc8>3.0.co;2-0
Subject(s) - solvation , ligand (biochemistry) , binding energy , chemistry , hydrogen bond , computer science , physics , statistical physics , computational chemistry , molecule , atomic physics , organic chemistry , biochemistry , receptor
We have developed B LEEP (biomolecular ligand energy evaluation protocol), an atomic level potential of mean force (PMF) describing protein–ligand interactions. Here, we present four tests designed to assess different attributes of B LEEP . Calculating the energy of a small hydrogen‐bonded complex allows us to compare B LEEP 's description of this system with a quantum‐chemical description. The results suggest that B LEEP gives an adequate description of hydrogen bonding. A study of the relative energies of various heparin binding geometries for human basic fibroblast growth factor (bFGF) demonstrates that B LEEP 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 B LEEP 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; B LEEP 's good performance here illustrates its ability to determine the relative energies of a series of similar complexes. We find that a protocol for incorporating solvation does not improve correlation with experiment. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 1177–1185, 1999