COMPUTATION OF ELECTROSTATIC COMPLEMENTS TO PROTEINS - A CASE OF CHARGE STABILIZED BINDING

Recent evidence suggests that the net effect of electrostatics is gene rally to destabilize protein binding due to large desolvation penaltie s. A novel method for computing ligand-charge distributions that optim ize the tradeoff between ligand desolvation penalty and favorable inte ractions with a binding site has been applied to a model for barnase. The result is a ligand-charge distribution with a favorable electrosta tic contribution to binding due, in part, to ligand point charges whos e direct interaction with the binding site is unfavorable, but which m ake strong intra-molecular interactions that are uncloaked on binding and thus act to lessen the ligand desolvation penalty.