Abstract
This chapter reviews the subject of noncovalent interactions in proteins with particular emphasis on the so-called weakly polar interactions. The chapter discusses the physical bases of the noncovalent electrostatic interactions that stabilize protein structure and the four types of weakly polar interactions that have been shown to occur in proteins are described with reference to some biologically significant examples of protein structure stabilization and protein–ligand binding. Atomic multipoles are estimated by fitting the atomic multipole expansion to the detailed features of the ground-state wave function obtained from ab initio quantum mechanical calculations. The amino acids phenylalanine, tyrosine, and tryptophan are traditionally grouped because their side chains are aromatic. The weakly polar nature of aromatic residues that leads to their interaction with oxygen and sulfur atoms suggests that they ought to be able to interact with themselves as well. Aromatic–aromatic interactions also play an important role in protein–ligand binding. The physical characteristics of noncovalent electrostatic interactions that stabilize protein structure have been described. In addition, an unusual group of weak electrostatic interactions in proteins, which have only recently been characterized, have been reviewed in detail and some examples of biological importance cited. These interactions, termed “weakly polar,” result from the characteristic distribution of partial charges in some amino acid side chain moieties and involve interactions among electronic monopole, dipole, and quadrupole moments.