A simple and efficient dispersion correction to the Hartree–Fock theory (2): Incorporation of a geometrical correction for the basis set superposition error

Abstract One of the most challenging problems in computer-aided drug discovery is the accurate prediction of the binding energy between a ligand and a protein. For accurate estimation of net binding energy Δ E bind in the framework of the Hartree–Fock (HF) theory, it is necessary to estimate two additional energy terms; the dispersion interaction energy ( E disp ) and the basis set superposition error (BSSE). We previously reported a simple and efficient dispersion correction, E disp , to the Hartree–Fock theory (HF-D tq ). In the present study, an approximation procedure for estimating BSSE proposed by Kruse and Grimme, a geometrical counterpoise correction (gCP), was incorporated into HF-D tq (HF-D tq -gCP). The relative weights of the E disp (D tq ) and BSSE (gCP) terms were determined to reproduce Δ E bind calculated with CCSD(T)/CBS or /aug-cc-pVTZ (HF-D tq -gCP (scaled)). The performance of HF-D tq -gCP (scaled) was compared with that of B3LYP-D 3 (BJ)-bCP (dispersion corrected B3LYP with the Boys and Bernadi counterpoise correction (bCP)), by taking Δ E bind (CCSD(T)-bCP) of small non-covalent complexes as ‘a golden standard’. As a critical test, HF-D tq -gCP (scaled)/6-31G(d) and B3LYP-D 3 (BJ)-bCP/6-31G(d) were applied to the complex model for HIV-1 protease and its potent inhibitor, KNI-10033. The present results demonstrate that HF-D tq -gCP (scaled) is a useful and powerful remedy for accurately and promptly predicting Δ E bind between a ligand and a protein, albeit it is a simple correction procedure.