EA-Inventor: Using vHTS scoring functions for de novo design

CINF 74

Robert S. Pearlman and Karl M. Smith. Optive Research, Inc, 12331-A Riata Trace Parkway -- Suite 110, Austin, TX 78727
Virtual HTS involves application of a scoring function to a specified, pre-determined set of structures. De novo design involves application of a scoring function to a dynamically evolving set of structures. De novo design also involves the application of a “structure modifying engine” to generate new structures and control the process by which structures with improved scores are evolved. Previous efforts to develop de novo design packages have focused, primarily, on developing “the best possible scoring function.” This is unfortunate for two reasons. First, the choice of “best” scoring function varies greatly from one discovery project to the next (and from one scientist to the next). Second, insufficient attention has been devoted to developing “the best possible structure modifying engine.”

We will describe an exceptionally complete and robust structure modifying engine (EA-Inventor) which offers two extremely important features. First, the nature of the structural modifications (and, hence, resulting structures) can be “tuned” to best suit the needs of particular discovery projects. Second, the engine can easily be used in conjunction with literally any scoring function or composite scoring function – whatever function is deemed most appropriate for the particular discovery project.