Electrostatic effects in hemoglobin: electrostatic energy associated with allosteric transition and effector binding

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Abstract
The pH dependence of the summed electrostatic stabilization for deoxy- and liganded Hb was computed for several ionic strength values. The computed contribution to the stabilization of deoxyHb by binding of 2,3-diphosphoglycerate in the .beta. cleft compared well with experimental binding behavior for human Hb AO and Hb F. The contribution of diphosphoglycerate binding to the alkaline Bohr effect was computed correctly for both Hb AO and F. The computed effects of simultaneous binding of diphosphoglycerate and formation of Val-1.beta. carbamino adducts suggested a competition between these effectors. A direct competition was formulated between these 2 effectors, with extension to include a simple anion such as chloride or bicarbonate binding in competition with diphosphoglycerate but not with Val-1.beta. carbamino formation. This model held at pH 7.3-7.4 over a range of concentrations of the effectors involved and predicted the pH dependence of Val-1.beta. carbamino formation over the pH range 7.0-8.0. The pH dependence of the computed differential stability of liganded vs. unliganded Hb A compared well with observation.