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.