OPTIMIZATION OF THE ELECTROSTATIC INTERACTIONS BETWEEN IONIZED GROUPSAND PEPTIDE DIPOLES IN PROTEINS

The three-dimensional optimization of the electrostatic interactions b etween the charged amino acid residues and the peptide partial charges was studied by Monte-Carlo simulations on a set of 127 nonhomologous protein structures with known atomic coordinates. It was shown that th is type of interaction is very well optimized for all proteins in the data pet, which suggests that they are a valuable driving force, at le ast for the native side-chain (c)onformations. Similar to the optimiza tion of the charge-charge interactions (Spassov VZ, Karshikoff AD, Lad enstein R, 1995, Protein Sci 4:1516-1527). the optimization effect was found more pronounced for enzymes than for proteins without enzymatic function. The asymmetry in the interactions of acidic and basic group s with the peptide dipoles was analyzed and a hypothesis was proposed that the properties of peptide dipoles are a factor contributing to th e natural selection of the basic amino acids in the chemical compositi on of proteins.