Here we describe studies in which high-level computational techniques, including symmetry adapeted perturbation theory (SAPT) analysis, are used to characterize the strength and character of R-X...π halogen bonds derived from protein-ligand structures found in the protein data bank (PDB). It is found that the strengths of these interactions can be significant, with interaction energies approaching those of common hydrogen bonds (~5 kcal/mol). The strength of these interactions strongly depends on the size and charge of the halogen σ-hole, as dictated by the halogen's chemical environment, but does not strongly correlate with the interaction's geometric parameters. SAPT analysis shows that, as might be expected, these interactions are strongly dependent on dispersion forces, while electrostatics also play a substatial role in stabilizing the complexes. In general, variations in binding energies between complexes depend strongly on modulation of the electrostatic interaction component.

High-level characterization of the properties of R-X...π interactions in protein-ligand complexes

253rd National Meeting (2017)

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