Evaluation of the FLEXX incremental construction algorithm for protein-ligand docking

We report on a test of FLEXX, a fully automatic docking tool for flexible L igands, on a highly diverse data set of 200 protein-ligand complexes from t he Protein Data Bank. In total 46.5% of the complexes of the data set can b e reproduced by a FLEXX docking solution at rank 1 with an rms deviation (R MSD) from the observed structure of less than 2 Angstrom. This rate rises t o 70% if one looks at the entire generated solution set. FLEXX produces rel iable results for ligands with up to 15 components which can be docked in 8 0% of the cases with acceptable accuracy. Ligands with more than 15 compone nts tend to generate wrong solutions more often, The average runtime of FLE XX on this test set is 93 seconds per complex on a SUN Ultra-30 workstation . In addition, we report on "cross-docking" experiments, in which several r eceptor structures of complexes with identical proteins have been used for docking all cocrystallized ligands of these complexes. In most cases, these experiments show that FLEXX can acceptably dock a Ligand into a foreign re ceptor structure. Finally we report on screening runs of ligands out of a l ibrary with 556 entries against ten different proteins. In eight cases FLEX X is able to find the original inhibitor within the top 7% of the total lib rary. Proteins 1999;37:228-241. (C) 1999 Wiley-Liss, Inc.