BOMB Version 2.4

BOMB (Biochemical and Organic Model Builder) is a key new software system, which is used to construct individual structures or combinatorial libraries given a selected core and substituents. The analogs are either built by themselves or inside a binding site. An extensive conformational search is performed using conformer information, which is stored for each substituent. Each conformer is optimally positioned in the binding site, and the lowest-energy structure for each analog is output as a PDB file or BOSS/MCPRO Z-matrix. The structure optimization is performed with the OPLS-AA force field, and then adjustable scoring functions are used to predict binding affinities or activities. BOMB typically requires between 3 seconds and 1 minute on a 2 GHz Pentium to process one analog-protein complex depending on the number of torsional degrees of freedom. The analogs have all principal torsion angles variable, while the host can be rigid or partially flexible. The output from BOMB includes a CSV file with a row for each analog containing its predicted activities, protein-analog energetic and structural results from BOMB, and QikProp results. The BOMB libraries contain more than 100 cores and 500 substituents, and molecules can be built in five topologies. The virtual library covers ca. 10 trillion molecules. QikProp is fully integrated with BOMB to filter designed molecules to have properties that fall inside user-defined ranges.

Celecoxib/COX-2 complex from BOMB. BOMB predicted vs experimental activities.