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.

对称适配扰动理论（Symmetry-adapted perturbation theory, SAPT）是一种分析分子间相互作用的宝贵方法。功能团 SAPT 分区（Functional group SAPT partition, F-SAPT）的引入，旨在为非共价相互作用的起源提供额外的洞察。迄今为止，SAPT 分析对于可能提供关键见解以改善配体结合的较大配体-蛋白质复合物而言，成本过高。在本文中，我们提出了一种 F-SAPT 变体的规模化实现。一开始便做出两项实用选择以使问题易于处理：（1）将离散和交换-离散的从头计算替换为 Grimme 的经验性离散校正。（2）避免具有扩展函数的基组，以便进行高效的积分筛选。这些选择使得 F-SAPT 分析主要可以以库仑和交换矩阵构建的形式编写，而这些构建已经在图形处理单元（GPUs）上高效实现。我们提出的 F-SAPT 公式可常规应用于含有超过 3000 个原子和 25,000 个基函数的分子，并且特别针对一个单体显著大于另一个单体的情况进行了优化。这一点通过使用极化双ζ基组对全型丁那韦（indinavir）@ HIV-II 蛋白酶复合物（PDB ID 1HSG）进行 F-SAPT 分析的结果得到了明确证明。