Physical Mechanisms Governing Substituent Effects on Arene-Arene Interactions in a Protein Milieu.

ABSTRACT: Arene-arene interactions play important roles in protein-ligand complex formation. Here, we investigate the characteristics of arene-arene interactions between small organic molecules and aromatic amino acids in protein interiors. The study is based on X-ray crystallographic data and quantum mechanical calculations using the enzyme acetylcholinesterase and selected inhibitory ligands as a model system. It is shown that the arene substituents of the inhibitors dictate the strength of the interaction and the geometry of the resulting complexes. Importantly, the calculated interaction energies correlate well with the measured inhibitor potency. Non-hydrogen substituents strengthened all interaction types in the protein milieu, in keeping with results for benzene dimer model systems. The inter

SUBMITTER: Andersson CD 

PROVIDER: S-EPMC7467712 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature