Enhanced docking with the mining minima optimizer: Acceleration and side-chain flexibility
- 9 October 2002
- journal article
- research article
- Published by Wiley in Journal of Computational Chemistry
- Vol. 23 (16) , 1656-1670
- https://doi.org/10.1002/jcc.10168
Abstract
The ligand–protein docking algorithm based on the Mining Minima method has been substantially enhanced. First, the basic algorithm is accelerated by: (1) adaptively determining the extent of each energy well to help avoid previously discovered energy minima; (2) biasing the search away from ligand positions at the surface of the receptor to prevent the ligand from staying at the surface when large sampling regions are used; (3) quickly testing multiple different ligand positions and orientations for each ligand conformation; and (4) tuning the source code to increase computational efficiency. These changes markedly shorten the time needed to discover an accurate result, especially when large sampling regions are used. The algorithm now also allows user‐selected receptor sidechains to be treated as mobile during the docking procedure. The energies associated with the mobile side chains are computed as if they belonged to the ligand, except that atoms at the boundary between side chains and the rigid backbone are treated specially. This new capability is tested for several well‐known ligand/protein systems, and preliminary application to an enzyme whose substrate is unknown—the recently solved hypothetical protein YecO (HI0319) from Haemophilus influenzae—indicates that side‐chains relaxations allow candidate substrates of various sizes to be accommodated. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1656–1670, 2002Keywords
This publication has 49 references indexed in Scilit:
- KEGG: Kyoto Encyclopedia of Genes and GenomesNucleic Acids Research, 2000
- The Protein Data BankNucleic Acids Research, 2000
- All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of ProteinsThe Journal of Physical Chemistry B, 1998
- Development and validation of a genetic algorithm for flexible docking 1 1Edited by F. E. CohenJournal of Molecular Biology, 1997
- Molecular docking to ensembles of protein structures 1 1Edited by B. HonigJournal of Molecular Biology, 1997
- Planar Stacking Interactions of Arginine and Aromatic Side-Chains in ProteinsJournal of Molecular Biology, 1994
- Validation of the general purpose QUANTA ®3.2/CHARMm® force fieldJournal of Computational Chemistry, 1992
- Refinement of the influenza virus hemagglutinin by simulated annealingJournal of Molecular Biology, 1990
- CHARMM: A program for macromolecular energy, minimization, and dynamics calculationsJournal of Computational Chemistry, 1983
- The protein data bank: A computer-based archival file for macromolecular structuresJournal of Molecular Biology, 1977