Large-Scale Functional Group Symmetry-Adapted Perturbation Theory on Graphical Processing Units

Symmetry-adapted perturbation theory (SAPT) is a valuable method for analyzing intermolecular interactions. The functional group SAPT partition (F-SAPT) has been introduced to provide additional insight into the origins of noncovalent interactions. Until now, SAPT analysis has been too costly for large ligand–protein complexes where it could provide key insights for chemical modifications that might improve ligand binding. In this paper, we present a large-scale implementation of a variant of F-SAPT. Two pragmatic choices are made from the outset to render the problem tractable: (1) Ab initio computation of dispersion and exchange-dispersion is replaced with Grimme’s empirical dispersion correction. (2) Basis sets with augmented functions are avoided to allow for efficient integral screening. These choices allow the F-SAPT analysis to be written largely in terms of Coulomb and exchange matrix builds which have been implemented efficiently on graphical processing units (GPUs). Our formulation of F-SAPT is routinely applicable to molecules with well over 3000 atoms and 25,000 basis functions and is particularly optimized for the case where one monomer is significantly larger than the other. This is demonstrated explicitly with results from F-SAPT analysis of the full indinavir @ HIV-II protease complex (PDB ID 1HSG) in a polarized double-ζ basis.