Importance of accurate docking for potency prediction


Colin McMartin, Thistlesoft, 603 Colebrook Road, Colebrook, CT 06021
Potency prediction of docked ligands depends not only on scoring but also on reliable docked geometries. Two different algorithms for thorough docking will be described. The first (MCDOCK) uses mutiple cycles of fast grid-box screened Monte Carlo searching. The search starts broadly and becomes progressively focused. The second method (ZIPDOCK) is near systematic. It uses a conformer compression algorithm to allow millions of docking poses to be screened in less than a minute. Both methods output multiple poses optimized in the binding site (full cartesian). An important feature is that selected parts of the site can move. Multiple docking poses were used to derive a new scoring function (CONTACT). Choice of docking method and number of rotatable bonds are found to have critical effects on the scores. Combining both docking methods significantly improves scores for flexible ligands.

Docking and Scoring
9:00 AM-12:20 PM, Monday, August 23, 2004 Pennsylvania Convention Center -- 109A, Oral

Division of Computers in Chemistry

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