Strength and Character of R-X…π Interactions Involving Aromatic Amino Acid Sidechains in Protein-Ligand Complexes Derived from Crystal Structures in the Protein Data Bank
National Science Foundation, National Institutes of Health
Department of Chemistry
Here, we investigate the strengths of R-X…π interactions, involving both chlorine and bromine, in model systems derived from protein-ligand complexes found in the PDB. We find that the strengths of these interactions can vary significantly, with binding energies ranging from −2.01 to −3.60 kcal/mol. Symmetry adapted perturbation theory (SAPT) analysis shows that, as would be expected, dispersion plays the largest role in stabilizing these R-X…π interactions, generally accounting for about 50% to 80% of attraction. R-Br…π interactions are, for the most part, found to be stronger than R-Cl…π interactions, although the relative geometries of the interacting pair and the halogen’s chemical environment can also have a strong impact. The two factors that have the strongest impact on the strength of these R-X…π interactions is the distance between the halogen and the phenyl plane as well as the size of the halogen σ-hole.
Riley, K E. and Tran, K A., "Strength and Character of R-X…π Interactions Involving Aromatic Amino Acid Sidechains in Protein-Ligand Complexes Derived from Crystal Structures in the Protein Data Bank" (2017). Faculty and Staff Publications. 101.