OPTIMIZATION OF THE ELECTROSTATIC INTERACTIONS IN PROTEINS OF DIFFERENT FUNCTIONAL AND FOLDING TYPE

The 3-dimensional optimization of the electrostatic interactions betwe en the charged amino acid residues was studied by Monte Carlo simulati ons on an extended representative set of 141 protein structures with k nown atomic coordinates. The proteins were classified by different fun ctional and structural criteria, and the optimization of the electrost atic interactions was analyzed. The optimization parameters were obtai ned by comparison of the contribution of charge-charge interactions to the free energy of the native protein structures and for a large numb er of randomly distributed charge constellations obtained by the Monte Carlo technique. On the basis of the results obtained, one can conclu de that the charge-charge interactions are better optimized in the enz ymes than in the proteins without enzymatic functions. Proteins that b elong to the mixed alpha beta folding type are electrostatically bette r optimized than pure alpha-helical or beta-strand structures. Protein s that are stabilized by disulfide bonds show a lower degree of electr ostatic optimization. The electrostatic interactions in a native prote in are effectively optimized by rejection of the conformers that lead to repulsive charge-charge interactions. Particularly, the rejection o f the repulsive contacts seems to be a major goal in the protein foldi ng process. The dependence of the optimization parameters on the choic e of the potential function was tested. The majority of the potential functions gave practically identical results.