Methods of consensus scoring for in silico screening


Kim M Branson, Joint Protein Structure Laboratory, The Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Royal Parade, Parkville, Melbourne, Australia and Brian J Smith, Structural Biology, The Walter and Eliza Hall Institute for Medical Research, Royal Melbourne Hospital, Royal Parade, Parkville, Melbourne, Australia.
Consensus methods[1-4] combine various scoring functions for in silico screening of large chemical databases against protein targets. They have been demonstrated to provide improved accuracy in the docking procedure, both the prediction of binding conformations and relative binding energies. We address here the issue of determining which scoring functions should be combined to obtain optimal results from the docking procedure. We illustrate this with examples where including too many scoring functions leads to a reduced hit-rate than when a select set of functions are used, and present a method of determining the best combination of functions to apply without the use of previously known ligands. The scoring functions used in the current analysis include DOCK, AutoDock, PMF, ChemScore, Score, SmoG. and X-cscore functions.

1. Bissantz C, Folkers G, Rognan D. Protein-based virtual screening of chemical databases. 1. Evaluation of different docking/scoring combinations. J Med Chem 2000 Dec 14;43(25):4759-67 2. Wang R, Wang S. How does consensus scoring work for virtual library screening? An idealized computer experiment. J Chem Inf Comput Sci 2001 Sep-Oct;41(5):1422-6 3. Wang R, Lai L, Wang S. Further development and validation of empirical scoring functions for structure-based binding affinity prediction. J Comput Aided Mol Des 2002 Jan;16(1):11-26 4. Clark RD, Strizhev A, Leonard JM, Blake JF, Matthew JB. Consensus scoring for ligand/protein interactions. J Mol Graph Model 2002 Jan;20(4):281-95


Docking and Scoring
1:30 PM-5:20 PM, Sunday, August 22, 2004 Pennsylvania Convention Center -- 109B, Oral

Division of Computers in Chemistry

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004