Extension of an Atom–Atom Dispersion Function to Halogen Bonds and Its Use for Rational Design of Drugs and Biocatalysts

[Image: see text] A dispersion function D(as) in the form of a damped atom–atom asymptotic expansion fitted to ab initio dispersion energies from symmetry-adapted perturbation theory was improved and extended to systems containing heavier halogen atoms. To illustrate its performance, the revised D(as) function was implemented in the multipole first-order electrostatic and second-order dispersion (MED) scoring model. The extension has allowed applications to a much larger set of biocomplexes than it was possible with the original D(as). A reasonable correlation between MED and experimentally determined inhibitory activities was achieved in a number of test cases, including structures featuring nonphysically shortened intermonomer distances, which constitute a particular challenge for binding strength predictions. Since the MED model is also computationally efficient, it can be used for reliable and rapid assessment of the ligand affinity or multidimensional scanning of amino acid side-chain conformations in the process of rational design of novel drugs or biocatalysts.