How a repulsive charge distribution becomes attractive and stabilized by a polarizable protein dielectric

摘要

Electrostatic energies (U) arising from sources of non-bonded interactions and their components from fixed charges (U_f) and induced dipoles (U_b) are calculated for the protein cytochrome P450 and its different substrate bound complexes. U_f is further broken up into charge-charge (U_(c-c)), charge-dipole (U_(c-d)) and dipole-dipole (U_(d-d)) interactions. It is found that charge-charge interaction is always repulsive and is much smaller in magnitude than the attractive interaction between permanent dipoles. Charge-dipole interaction is smaller in magnitude than both these interactions and is attractive in some proteins and repulsive in others. The energy changes on charging a protein are calculated and it is found that energy is lowered as a result of charging. Even though the charge-charge interaction in these proteins are repulsive, other interactions cause a lowering of energy on charging. The mutually repelling distribution of free charges is stabilized by the polarizable protein dielectric and become attractive. An effective screening constant for the charge-charge interactions in the protein dielectric turns out to be negative. The high sensitivity of these quantities to small structural changes on ligand binding reestablish the importance of electrostatics on protein dynamics.