Enhanced docking with the mining minima optimizer: Acceleration and side-chain flexibility Export

@article{citeulike:771541, 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. {\copyright} 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1656-1670, 2002}, address = {Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, 9600 Gudelsky Dr., Rockville, Maryland 20850}, author = {Kairys, Visvaldas and Gilson, Michael K.}, citeulike-article-id = {771541}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/jcc.10168}, citeulike-linkout-1 = {http://www3.interscience.wiley.com/cgi-bin/abstract/99018400/ABSTRACT}, doi = {10.1002/jcc.10168}, journal = {Journal of Computational Chemistry}, keywords = {cross\_docking, docking, ga, search}, number = {16}, pages = {1656--1670}, posted-at = {2007-01-03 21:51:37}, priority = {2}, title = {Enhanced docking with the mining minima optimizer: Acceleration and side-chain flexibility}, url = {http://dx.doi.org/10.1002/jcc.10168}, volume = {23}, year = {2002} }

TY - JOUR ID - citeulike:771541 L3 - citeulike-article-id:771541 N2 - 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, 2002 IS - 16 JF - Journal of Computational Chemistry AD - Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, 9600 Gudelsky Dr., Rockville, Maryland 20850 EP - 1670 TI - Enhanced docking with the mining minima optimizer: Acceleration and side-chain flexibility VL - 23 SP - 1656 KW - cross_docking KW - docking KW - ga KW - search AU - Kairys, Visvaldas AU - Gilson, Michael PY - 2002/// UR - http://dx.doi.org/10.1002/jcc.10168 ER -