Andersson_2020_J.Phys.Chem.B_124_6529

Reference

Title : Physical Mechanisms Governing Substituent Effects on Arene-Arene Interactions in a Protein Milieu - Andersson_2020_J.Phys.Chem.B_124_6529
Author(s) : Andersson CD , Mishra BK , Forsgren N , Ekstrom F , Linusson A
Ref : J Phys Chem B , 124 :6529 , 2020
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 interaction energies were dispersion-dominated, but substituents that induced local dipole moments increased the electrostatic contribution and thus yielded more strongly bound complexes. These findings provide fundamental insights into the physical mechanisms governing arene-arene interactions in the protein milieu and thus into molecular recognition between proteins and small molecules.

PubMedSearch : Andersson_2020_J.Phys.Chem.B_124_6529
PubMedID: 32610016
Gene_locus related to this paper: mouse-ACHE

Related information

Inhibitor CHEMBL3087809
Gene_locus CHEMBL3087809    mouse-ACHE
Structure CHEMBL3087809    mouse-ACHE    6TD2

Citations formats

Andersson CD, Mishra BK, Forsgren N, Ekstrom F, Linusson A (2020)
Physical Mechanisms Governing Substituent Effects on Arene-Arene Interactions in a Protein Milieu
J Phys Chem B 124 :6529

Andersson CD, Mishra BK, Forsgren N, Ekstrom F, Linusson A (2020)
J Phys Chem B 124 :6529