Electrostatic interactions, in protein

We review the subject of noncovalent interactions in proteins with particular emphasis on the so-called weakly polar interactions. First, the physical bases of the noncovalent electrostatic interactions that stabilize protein structure are discussed. Second, 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. Third, hydrophobic effects in proteins are discussed. Fourth, an hypothesis regarding the biological importance of the weakly polar interaction is advanced. Finally, we propose adoption of a systematic classification of electrostatic interactions in proteins. 

If a charge distribution p(r) is placed in an electric field [ J (r)] due to a second nonoverlapping charge distribution, p (r), the electrostatic potential energy of the system is given by 

When the charge distributions correspond to molecules such as proteins that are composed of discrete segments, i.e., atoms, the charge distribution function can be expressed as the sum of atomic charge densities given by 

Further simplification is achieved by rewriting the potential function 4 (r) as a Taylor series expansion about the origin  

Once the electronic multipole moments have been identified as q, net charge /t, dipole moment etc. the above expression for the electrostatic energy becomes 

---

Niedermeier, C, Tavan, P. A structure-adapted multipole method for electrostatic interactions in protein dynamics. J. chem. Phys. 101 (1994) 734-748. 

Here Vij denotes the distance between atoms i and j and g(i) the type of the amino acid i. The Leonard-Jones parameters Vij,Rij for potential depths and equilibrium distance) depend on the type of the atom pair and were adjusted to satisfy constraints derived from as a set of 138 proteins of the PDB database [18, 17, 19]. The non-trivial electrostatic interactions in proteins are represented via group-specific dielectric constants ig(i),g(j) depending on the amino-acid to which atom i belongs). The partial charges qi and the dielectric constants were derived in a potential-of-mean-force approach [20]. Interactions with the solvent were first fit in a minimal solvent accessible surface model [21] parameterized by free energies per unit area (7j to reproduce the enthalpies of solvation of the Gly-X-Gly family of peptides [22]. Ai corresponds to the area of atom i that is in contact with a ficticious solvent. Hydrogen bonds are described via dipole-dipole interactions included in the electrostatic terms... 

Nakamura HQ (1996) Roles of electrostatic interactions in proteins, Rev Biophys, 29 1-90... 

Contributions from Electronic Polarizability to Electrostatic Interactions in Proteins. ... 

Warshel, A., Russell, S.T. and Churg, A.K. (1984). Macroscopic models for studies of electrostatic interactions in proteins limitations and applicability. Proc. Natl. Acad. Sci. USA 81, 4785 4789... 

Protein segments adopt only a finite number of conformations in folded proteins.This limited dictionary of templates may be due to the inherent steric constraints of the backbone and other packing and electrostatic interactions in protein folding. This was most graphically demonstrated by Jones and Thirup. They showed that the majority of the polypeptide backbone of a new structure can be built up from component pieces of other structures, whether or not they are related. Unger et al. showed, in fact, that 76% of the main chain structure of an 82 protein data set can be constructed using only 100 unique hexapeptide templates. Amino acid side chains are also found in a restricted set of conformers. Recent work in our laboratory has shown that a set of four tetrapeptide templates is sufficient to define almost all loop conformations. 

A. Warshel, S. T. Russell, and A. K. Churg, Proc. Natl. Acad. Set. U.S.A., 81,4785 (1984). Macroscopic Models for Studies of Electrostatic Interactions in Proteins Limitations and Applicability. 

---