caa a22 4500 467939063 CHVBK 20180406153006.0 cr unu---uuuuu 170328e20061001xx s 000 0 eng 10.1007/s10822-006-9060-4 doi (NATIONALLICENCE)springer-10.1007/s10822-006-9060-4 Development and validation of a modular, extensible docking program: DOCK 5 [Elektronische Daten] [Demetri Moustakas, P. Lang, Scott Pegg, Eric Pettersen, Irwin Kuntz, Natasja Brooijmans, Robert Rizzo] We report on the development and validation of a new version of DOCK. The algorithm has been rewritten in a modular format, which allows for easy implementation of new scoring functions, sampling methods and analysis tools. We validated the sampling algorithm with a test set of 114 protein-ligand complexes. Using an optimized parameter set, we are able to reproduce the crystal ligand pose to within 2 Å of the crystal structure for 79% of the test cases using our rigid ligand docking algorithm with an average run time of 1min per complex and for 72% of the test cases using our flexible ligand docking algorithm with an average run time of 5min per complex. Finally, we perform an analysis of the docking failures in the test set and determine that the sampling algorithm is generally sufficient for the binding pose prediction problem for up to 7 rotatable bonds; i.e. 99% of the rigid ligand docking cases and 95% of the flexible ligand docking cases are sampled successfully. We point out that success rates could be improved through more advanced modeling of the receptor prior to docking and through improvement of the force field parameters, particularly for structures containing metal-based cofactors. Springer Science+Business Media B.V., 2006 Automated docking nationallicence Scoring functions nationallicence Structure-based drug design nationallicence Flexible docking nationallicence Binding mode prediction nationallicence Incremental construction nationallicence Validation nationallicence Moustakas Demetri Joint Graduate Program in Bioengineering, University of California, San Francisco, 600 16th Street, Genentech Hall, Box 2240, 94143, San Francisco, CA, USA aut Lang P. Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, 600 16th Street, Genentech Hall, Box 2240, 94143, San Francisco, CA, USA aut Pegg Scott Department of Pharmaceutical Chemistry, University of California, San Francisco, 600 16th Street, Genentech Hall, Box 2240, 94143, San Francisco, CA, USA aut Pettersen Eric Department of Pharmaceutical Chemistry, University of California, San Francisco, 600 16th Street, Genentech Hall, Box 2240, 94143, San Francisco, CA, USA aut Kuntz Irwin Department of Pharmaceutical Chemistry, University of California, San Francisco, 600 16th Street, Genentech Hall, Box 2240, 94143, San Francisco, CA, USA aut Brooijmans Natasja Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, 600 16th Street, Genentech Hall, Box 2240, 94143, San Francisco, CA, USA aut Rizzo Robert Department of Applied Mathematics and Statistics, Stony Brook University, Room 1-101, 11794-3600, Stony Brook, NY, USA aut Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/10-11(2006-10-01), 601-619 0920-654X 20:10-11<601 2006 20 10822 https://doi.org/10.1007/s10822-006-9060-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10822-006-9060-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Moustakas Demetri Joint Graduate Program in Bioengineering, University of California, San Francisco, 600 16th Street, Genentech Hall, Box 2240, 94143, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Lang P. Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, 600 16th Street, Genentech Hall, Box 2240, 94143, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Pegg Scott Department of Pharmaceutical Chemistry, University of California, San Francisco, 600 16th Street, Genentech Hall, Box 2240, 94143, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Pettersen Eric Department of Pharmaceutical Chemistry, University of California, San Francisco, 600 16th Street, Genentech Hall, Box 2240, 94143, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Kuntz Irwin Department of Pharmaceutical Chemistry, University of California, San Francisco, 600 16th Street, Genentech Hall, Box 2240, 94143, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Brooijmans Natasja Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, 600 16th Street, Genentech Hall, Box 2240, 94143, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Rizzo Robert Department of Applied Mathematics and Statistics, Stony Brook University, Room 1-101, 11794-3600, Stony Brook, NY, USA aut NATIONALLICENCE 773 0- Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/10-11(2006-10-01), 601-619 0920-654X 20:10-11<601 2006 20 10822 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer