A preference for edgewise interactions between aromatic rings and carboxylate anions: the biological relevance of anion-quadrupole interactions

J Phys Chem B. 2007 Jul 19;111(28):8242-9. doi: 10.1021/jp0661995. Epub 2007 Jun 20.

Abstract

Noncovalent interactions are quite important in biological structure-function relationships. To study the pairwise interaction of aromatic amino acids (phenylalanine, tyrosine, tryptophan) with anionic amino acids (aspartic and glutamic acids), small molecule mimics (benzene, phenol or indole interacting with formate) were used at the MP2 level of theory. The overall energy associated with an anion-quadrupole interaction is substantial (-9.5 kcal/mol for a benzene-formate planar dimer at van der Waals contact distance), indicating the electropositive ring edge of an aromatic group can interact with an anion. Deconvolution of the long-range coplanar interaction energy into fractional contributions from charge-quadrupole interactions, higher-order electrostatic interactions, and polarization terms was achieved. The charge-quadrupole term contributes between 30 to 45% of the total MP2 benzene-formate interaction; most of the rest of the interaction arises from polarization contributions. Additional studies of the Protein Data Bank (PDB Select) show that nearly planar aromatic-anionic amino acid pairs occur more often than expected from a random angular distribution, while axial aromatic-anionic pairs occur less often than expected; this demonstrates the biological relevance of the anion-quadrupole interaction. While water may mitigate the strength of these interactions, they may be numerous in a typical protein structure, so their cumulative effect could be substantial.

MeSH terms

  • Amino Acids, Aromatic / chemistry*
  • Amino Acids, Dicarboxylic / chemistry*
  • Benzene / chemistry
  • Chemistry, Physical / methods*
  • Energy Transfer
  • Formates / chemistry
  • Hydrogen Bonding
  • Ligands
  • Protein Folding
  • Proteins / chemistry*
  • Quantum Theory

Substances

  • Amino Acids, Aromatic
  • Amino Acids, Dicarboxylic
  • Formates
  • Ligands
  • Proteins
  • formic acid
  • Benzene