Hierarchical docking of databases of multiple ligand conformations. Export

@article{citeulike:322022, abstract = {Ligand flexibility is an important problem in molecular docking and virtual screening. To address this challenge, we investigate a hierarchical pre-organization of multiple conformations of small molecules. Such organization of pre-calculated conformations removes the exploration of ligand conformational space from the docking calculation and allows for concise representation of what can be thousands of conformations. The hierarchy also recognizes and prunes incompatible conformations early in the calculation, eliminating redundant calculations of fit. We investigate the method by docking the MDL Drug Data Report (MDDR), an annotated database of 100,000 molecules, into apo and holo forms of seven unrelated targets. This annotated database allows us to track the ranking of tens to hundreds of annotated ligands in each of the docking systems. The binding sites and database are prepared in an automated fashion in an attempt to remove some human bias from the calculations. Many thousands of explicit and implicit ligand conformations may be docked in calculations not much longer than required for single conformer docking. As long as internal energies are not considered, recombination with the hierarchy is additive as the number of degrees of freedom is increased. Molecules with even millions of conformations can be docked in a few minutes on a single desktop computer.}, address = {University of California San Francisco, Dept. of Pharmaceutical Chemistry, 1700 4 Street, QB3 Building Room 508D, San Francisco, CA 94143-2550, USA.}, author = {Lorber, D. M. and Shoichet, B. K.}, citeulike-article-id = {322022}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/16101414}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=16101414}, comment = {pre-calculated ligand conformations.}, issn = {1568-0266}, journal = {Curr Top Med Chem}, keywords = {flex, ligand}, number = {8}, pages = {739--749}, posted-at = {2005-09-16 06:23:40}, priority = {2}, title = {Hierarchical docking of databases of multiple ligand conformations.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/16101414}, volume = {5}, year = {2005} }

TY - JOUR ID - citeulike:322022 L3 - citeulike-article-id:322022 N2 - Ligand flexibility is an important problem in molecular docking and virtual screening. To address this challenge, we investigate a hierarchical pre-organization of multiple conformations of small molecules. Such organization of pre-calculated conformations removes the exploration of ligand conformational space from the docking calculation and allows for concise representation of what can be thousands of conformations. The hierarchy also recognizes and prunes incompatible conformations early in the calculation, eliminating redundant calculations of fit. We investigate the method by docking the MDL Drug Data Report (MDDR), an annotated database of 100,000 molecules, into apo and holo forms of seven unrelated targets. This annotated database allows us to track the ranking of tens to hundreds of annotated ligands in each of the docking systems. The binding sites and database are prepared in an automated fashion in an attempt to remove some human bias from the calculations. Many thousands of explicit and implicit ligand conformations may be docked in calculations not much longer than required for single conformer docking. As long as internal energies are not considered, recombination with the hierarchy is additive as the number of degrees of freedom is increased. Molecules with even millions of conformations can be docked in a few minutes on a single desktop computer. IS - 8 JF - Curr Top Med Chem SN - 1568-0266 AD - University of California San Francisco, Dept. of Pharmaceutical Chemistry, 1700 4 Street, QB3 Building Room 508D, San Francisco, CA 94143-2550, USA. EP - 749 TI - Hierarchical docking of databases of multiple ligand conformations. VL - 5 SP - 739 KW - flex KW - ligand N1 - pre-calculated ligand conformations. AU - Lorber, DM AU - Shoichet, BK PY - 2005/// UR - http://view.ncbi.nlm.nih.gov/pubmed/16101414 ER -