Two different algorithms for core-constrained docking in Glide were compared: one is a filtering approach which has been supported since 2006 and is based on Glide's standard docking algorithm; the other is a new algorithm implemented in 2014 which follows a "snap and refine" approach combined with a partial conformational search. Both algorithms include a post-docking minimization step with a flat-bottom restraining potential, and both accept a target tolerance for the RMSD of the atoms defining the core. The pose yield (defined as the probability of a pose being reported) as a function of tolerance was determined for each algorithm using a set of 506 complexes with a total of 1094 different cores. The pose yield for the snap-and-refine algorithm was found to be 92% and is independent of tolerance. The pose yield for the filtering algorithm is very sensitive to the tolerance, ranging from 0% at zero tolerance to 96% at 1.0 Å and 100% at 100.0 Å (i.e., effectively infinite) tolerance. The two algorithms have the same pose yield at approximately 0.75 Å, which has been implemented in Glide as the cutoff for picking which algorithm to use by default given a user-specified tolerance.

Tolerance-dependent algorithm for core-constrained ligand docking with glide

249th National Meeting (2015)

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