BOMB for growing and scoring protein-ligand complexes

COMP 83

William L. Jorgensen and Julian Tirado-Rives. Department of Chemistry, Yale University, New Haven, CT 06520-8107
BOMB, Biochemical and Organic Model Builder, is used to rapidly construct and evaluate biomolecule-ligand complexes. Ligands are grown starting from a core that is positioned in the binding site. An extensive conformational search is performed for the ligand and each conformer is optimally positioned in the binding site. The structure optimization is performed with the OPLS-AA force field, and then scoring functions are used to predict binding affinities or activities by consideration of, for example, protein-ligand Coulomb and van der Waals interactions, hydrogen-bonding, and solvation. High speed follows from the use of internal coordinates for the search and optimizations. The ligands have all principal torsion angles variable, while the host can either be rigid or have side chains with flexible dihedral angles. The BOMB libraries contain more than 100 cores and 500 substituents, which are common drug fragments; the resulting virtual library covers ca. 10 trillion molecules. QikProp is fully integrated with BOMB to filter designed molecules to be druglike. Results of validation studies and applications to multiple protein targets will be presented.
 

Docking and Scoring
9:00 AM-12:20 PM, Tuesday, August 24, 2004 Pennsylvania Convention Center -- 109B, Oral

Division of Computers in Chemistry

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