Evaluation of docking strategies for virtual screening of compound databases: cAMP-dependent serine/threonine kinase...

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.