title: Evaluation of docking strategies for virtual screening of compound databases: cAMP-dependent serine/threonine kinase as an example.
abstract: In an effort to establish efficient docking routines for computational screening of compound databases on protein structures, cAMP-dependent protein kinase has been selected as a test case and a variety of docking options and scoring functions were compared. These included rigid-body and flexible docking and scoring based on surface complementarity and/or force field energy. Inhibitors were removed from complex crystal structures and added to compound libraries in their binding conformations and, in addition, deliberately modified conformations. Rigid-body docking and contact scoring well reproduced two of three experimental enzyme-inhibitor complexes. Ligand docking with flexible torsional angles failed to do so but anchored search of some inhibitors converged near to experimental structures, however, only when energy scoring was applied.
authors.affiliation: Computational Chemistry and Informatics, MDS Panlabs, Bothell, Washington 98011-8805, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Godden
authors.forename: F
authors.initials: F
authors.lastname: Stahura
authors.forename: J
authors.initials: J
authors.lastname: Bajorath
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000378:metabolism; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D016208:Databases, Factual; D004791:Enzyme Inhibitors / Q000378:metabolism; D005069:Evaluation Studies as Topic; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism; D015394:Molecular Structure; D011487:Protein Conformation; D013449:Sulfonamides
chemical_list: D004791:Enzyme Inhibitors; D007546:Isoquinolines; D013449:Sulfonamides; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide