A simple and efficient dispersion correction to the Hartree-Fock theory (3): A comprehensive performance comparison of HF-Dtq with MP2 and DFT-Ds.

Abstract Accurate prediction of the intermolecular interaction energy (Δ E bind ) has been a challenging and serious problem. Current in silico drug screening demands efficient and accurate evaluation of Δ E bind for ligands and their target proteins. It is desirable that Δ E bind including the dispersion interaction energy ( E disp ) is calculated using a post-Hartree–Fock (HF) theory, such as the high-order coupled-cluster one, with a larger basis set. However, it remains computationally too expensive to apply such a one to large molecular systems. As another problem, it is necessary to consider the contribution of the basis set superposition error (BSSE) in calculation of Δ E bind . In Bioorg. Med. Chem. Lett. 2014 and 2015, we proposed simple and efficient corrections of dispersion and BSSE for the HF theory, which is not able to express the dispersion interaction energy correctly. The current Letter, as the final one in the series, aims to verify the HF theory enhanced by the dispersion correction (HF-Dtq) in the light of reproducibility of ‘accurate’ intermolecular ligand–protein interaction energy values, with comprehensive comparison with the MP2 and recently proposed various DFT-D theories. Taking Δ E bind calculated with the coupled-cluster theory coupled with a complete basis set as a reference, Δ E bind of over a hundred small sized noncovalent complexes as well as real ligand–protein complexes models was systematically examined in terms of accuracy and computational cost. The comprehensive comparison in the current work showed that HF-Dtq is a practical and reliable approach for in silico drug screening and quantitative structure–activity relationships.