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B LEEP —potential of mean force describing protein–ligand interactions: I. Generating potential
Author(s) -
Mitchell John B. O.,
Laskowski Roman A.,
Alex Alexander,
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<1165::aid-jcc7>3.0.co;2-a
Subject(s) - protein ligand , ligand (biochemistry) , maxima and minima , polar , potential of mean force , hydrogen bond , chemistry , potential energy , physics , computational chemistry , crystallography , chemical physics , molecular dynamics , mathematics , atomic physics , molecule , quantum mechanics , receptor , mathematical analysis , biochemistry , organic chemistry
Abstract We have developed B LEEP (biomolecular ligand energy evaluation protocol), an atomic level potential of mean force (PMF) describing protein–ligand interactions. The pair potentials for B LEEP have been derived from high‐resolution X‐ray structures of protein–ligand complexes in the 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 B LEEP 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 B LEEP 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, around 3.0 Å, whereas a typical hydrophobic interaction is repulsive at this distance, with values above 4.0 Å being preferred. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 1165–1176, 1999