[17] Calculation of electrostatic interactions in proteins

Publisher Summary The chapter discusses methods for the calculation of electrostatic interactions in proteins. By use of the static accessibility modification of the Tanford–Kirkwood model, a simple and efficient computational procedure yields quantitative and qualitative results in agreement with experimental data. The assumption that the structure of the protein in solution throughout the pH range of interest is essentially that of the crystal seems to hold reasonably well. Minor perturbations occur in solution and alter charge configurations. The working electrostatic model for the protein molecule adapts easily to a variety of problems and enables one to evaluate electrostatic contributions to such diverse phenomena as the binding of charged ligands, amino acid substitutions of site-directed mutagens, and any known tertiary or quaternary structural change. The static-accessibility-modified theory has been successfully applied to a variety of proteins that include sperm whale myoglobin and 11 species variations, oxy- and to deoxyhemoglobins and their interactions involving hydrogen ions, chloride ions, carbamino adducts, and organic phosphate polyanions, Bovine pancreatic trypsin inhibitor (BPTI) and ribonuclease. The generality of this approach is illustrated by the fact that all computations are based on the same consistent set of intrinsic p K values with the appropriate solvent accessibility parameter obtained from the known atomic coordinates.