Docking flexible ligands to macromolecular receptors by molecular shape. Export

@article{citeulike:2267583, abstract = {We present a method to explore the interaction of flexible ligands with receptors of known geometry on the basis of molecular shape. This method is an extension of that described by Kuntz et al. (J. Mol. Biol. 1982, 161, 269). The shape of a binding site on a macromolecular receptor is represented as a set of overlapping spheres. Each ligand is divided into a small set of large rigid fragments that are docked separately into the binding site and then rejoined later in the calculation. The division of ligands into separate fragments allows a degree of flexibility at the position that joins them. The rejoined fragments are then energy minimized in the receptor site. We illustrate the method with two test cases: dihydrofolate reductase/methotrexate and prealbumin/thyroxine. For each test case, the method finds binding geometries for the ligand near that observed crystallographically as well as others that provide good steric fit with the receptor.}, author = {DesJarlais, R. L. and Sheridan, R. P. and Dixon, J. S. and Kuntz, I. D. and Venkataraghavan, R.}, citeulike-article-id = {2267583}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/3783576}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=3783576}, issn = {0022-2623}, journal = {J Med Chem}, keywords = {docking, flexible, fragment}, month = {November}, number = {11}, pages = {2149--2153}, posted-at = {2008-01-21 12:04:15}, priority = {2}, title = {Docking flexible ligands to macromolecular receptors by molecular shape.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/3783576}, volume = {29}, year = {1986} }

TY - JOUR ID - citeulike:2267583 L3 - citeulike-article-id:2267583 N2 - We present a method to explore the interaction of flexible ligands with receptors of known geometry on the basis of molecular shape. This method is an extension of that described by Kuntz et al. (J. Mol. Biol. 1982, 161, 269). The shape of a binding site on a macromolecular receptor is represented as a set of overlapping spheres. Each ligand is divided into a small set of large rigid fragments that are docked separately into the binding site and then rejoined later in the calculation. The division of ligands into separate fragments allows a degree of flexibility at the position that joins them. The rejoined fragments are then energy minimized in the receptor site. We illustrate the method with two test cases: dihydrofolate reductase/methotrexate and prealbumin/thyroxine. For each test case, the method finds binding geometries for the ligand near that observed crystallographically as well as others that provide good steric fit with the receptor. IS - 11 JF - J Med Chem SN - 0022-2623 EP - 2153 TI - Docking flexible ligands to macromolecular receptors by molecular shape. VL - 29 SP - 2149 KW - docking KW - flexible KW - fragment AU - DesJarlais, RL AU - Sheridan, RP AU - Dixon, JS AU - Kuntz, ID AU - Venkataraghavan, R PY - 1986/11// UR - http://view.ncbi.nlm.nih.gov/pubmed/3783576 ER -