SPATIAL OPTIMIZATION OF ELECTROSTATIC INTERACTIONS BETWEEN THE IONIZED GROUPS IN GLOBULAR-PROTEINS

A model approach is suggested to estimate the degree of spatial optimi zation of the electrostatic interactions in protein molecules. The met hod is tested on a set of 44 globular proteins, representative of the available crystallographic data. The theoretical model is based on mac roscopic computation of the contribution of charge-charge interactions to the electrostatic term of the free energy for the native proteins and for a big number of virtual structures with randomly distributed o n protein surface charge consetellations (generated by a Monte-Carlo t echnique). The statistical probability of occurrence of random structu res with electrostatic energies lower than the energy of the native pr otein is suggested as a criterion for spatial optimization of the elec trostatic interactions. The results support the hypothesis that the fo lding process optimizes the stabilizing effect of electrostatic intera ctions, but to very different degree for different proteins, A paralle l analysis of ion pairs shows that the optimization of the electrostat ic term in globular proteins has increasingly gone in the direction of rejecting the repulsive short contacts between charges of equal sign than of creating of more salt bridges (in comparison with the statisti cally expected number of short-range ion pairs in the simulated random structures). It is observed that the decrease in the spatial optimiza tion of the electrostatic interactions is usually compensated for by a n appearance of disulfide bridges in the covalent structure of the exa mined proteins. (C) 1991 Wiley-Liss, Inc.