Towards an understanding of the arginine-aspartate interaction

J Mol Biol. 1992 Jul 5;226(1):251-62. doi: 10.1016/0022-2836(92)90137-9.

Abstract

We have made a comparison of the geometries of intra- and intermolecular arginine-aspartate interactions by extracting orientation information from protein co-ordinate data. The results show a pronounced difference, with both types of interaction preferring to form twin N-H . . . O = C hydrogen bonds, but involving different nitrogen atoms. In intramolecular interactions, the aspartate favours a "side on" geometry, forming hydrogen bonds with N epsilon and N eta 2; in the intermolecular case, however, "end on" contacts involving N eta 1 and N eta 2 of the arginine are preferred. We have used Distributed Multipole Analysis of the methylguanidinium-acetate system to model the electrostatic component of the arginine-aspartate ion pair interaction in vacuo. We find, in agreement with the experimental arginine-aspartate distribution, that side on and end on doubly N-H . . . O = C hydrogen-bonded configurations are clearly the most favourable, with the side on being marginally lower in energy. Thus, despite the many competing side-chain interactions in proteins, many arginine-aspartate pairs adopt one of the minimum electrostatic energy conformations, or one close to a minimum. Within each of the two regions (side on and end on) we find only a small energy gap between the "symmetric" doubly hydrogen-bonded and slightly displaced "staggered" structures, again in agreement with the crystal structure data. Further calculations of the total ab initio interaction energy show that this follows the electrostatic term in its orientational variation, this phenomenon of "electrostatic domination" being well known in hydrogen-bonded systems. The end on arginine nitrogen atoms are observed to be more surface-exposed than N epsilon, as demonstrated by their greater accessibilities over a large sample of proteins. This helps explain the side on and end on preferences of intra- and intermolecular interactions, respectively. We also note the effect of short sequence intervals, particularly i in equilibrium with i + 2 relationships, in forcing many intramolecular contacts to be side on.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / chemistry*
  • Aspartic Acid / chemistry*
  • Computer Simulation*
  • Hydrogen Bonding
  • Macromolecular Substances
  • Models, Molecular
  • Nitrogen / chemistry
  • Proteins / chemistry*

Substances

  • Macromolecular Substances
  • Proteins
  • Aspartic Acid
  • Arginine
  • Nitrogen