Non-random ionic-charge distribution responsible for the structural stability and molecular recognition of proteins.

Abstract

The 'ionic-charge shuffling method' is presented to generate a complete set of electrostatic mutants for a natural protein where ionic charges on the molecular surface of the template protein are exhaustively interchanged with each other. Total Coulomb interaction energies are evaluated for all of the mutants by numerically solving the finite difference Poisson-Boltzmann equation and their distribution in the ensemble is obtained. This method has been applied to five natural proteins to reveal that they have a significantly lower Coulomb energy than the average over the ensemble of their mutants. It is also shown that these natural proteins have a significantly larger and smaller number of pairs of attractive and repulsive ionic groups, respectively, than those expected for their randomly shuffled ensemble: They have been 'designed' through molecular evolution so that a pair of ionic charges with opposite signs may have a higher tendency to be located close to each other, while a pair with the same sign are away from each other.