ProPose: steered virtual screening by simultaneous protein-ligand docking and ligand-ligand alignment. Export

@article{citeulike:2204898, abstract = {The 'model-free' screening engine ProPose implements a general method for performing simultaneous protein-ligand docking, ligand-ligand alignment, pharmacophore queries-and combinations thereof-in order to incorporate a priori information into screening protocols. In this manuscript we describe a case study on herpes simplex virus thymidine kinase, an important antiviral drug target, where we evaluate different approaches for handling a specific type of a priori information, i.e., multiple target structures. We demonstrate that a simultaneous alignment on two target structures--in conjunction with logic operations on interactions and docking constraints derived from protein structure--is an effective means of (i) improving the enrichment of chemical substructures that are compatible with the a priori known ligands, (ii) ensuring the steric fit into the target protein, and (iii) handling target flexibility. The combination of ligand- and receptor-based methods steers the virtual screening by ranking molecules according to the similarity of their interaction pattern with known ligands, thereby--to some extent--outweighing the deficiencies of simple scoring functions often used in initial virtual screening.}, address = {4SC AG, Am Klopferspitz 19a, D-82152 Martinsried, Germany. markus.seifert@4sc.com}, author = {Seifert, M. H.}, citeulike-article-id = {2204898}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/ci0496393}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/ci0496393}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/15807511}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=15807511}, doi = {10.1021/ci0496393}, issn = {1549-9596}, journal = {J Chem Inf Model}, keywords = {homdock}, number = {2}, pages = {449--460}, posted-at = {2008-01-22 09:44:45}, priority = {2}, title = {ProPose: steered virtual screening by simultaneous protein-ligand docking and ligand-ligand alignment.}, url = {http://dx.doi.org/10.1021/ci0496393}, volume = {45}, year = {2005} }

TY - JOUR ID - citeulike:2204898 L3 - citeulike-article-id:2204898 N2 - The 'model-free' screening engine ProPose implements a general method for performing simultaneous protein-ligand docking, ligand-ligand alignment, pharmacophore queries-and combinations thereof-in order to incorporate a priori information into screening protocols. In this manuscript we describe a case study on herpes simplex virus thymidine kinase, an important antiviral drug target, where we evaluate different approaches for handling a specific type of a priori information, i.e., multiple target structures. We demonstrate that a simultaneous alignment on two target structures--in conjunction with logic operations on interactions and docking constraints derived from protein structure--is an effective means of (i) improving the enrichment of chemical substructures that are compatible with the a priori known ligands, (ii) ensuring the steric fit into the target protein, and (iii) handling target flexibility. The combination of ligand- and receptor-based methods steers the virtual screening by ranking molecules according to the similarity of their interaction pattern with known ligands, thereby--to some extent--outweighing the deficiencies of simple scoring functions often used in initial virtual screening. IS - 2 JF - J Chem Inf Model SN - 1549-9596 AD - 4SC AG, Am Klopferspitz 19a, D-82152 Martinsried, Germany. markus.seifert@4sc.com EP - 460 TI - ProPose: steered virtual screening by simultaneous protein-ligand docking and ligand-ligand alignment. VL - 45 SP - 449 KW - homdock AU - Seifert, MH PY - 2005///r UR - http://dx.doi.org/10.1021/ci0496393 ER -