AJP - Cell Physiology, Vol 258, Issue 3 C563-C577, Copyright © 1990 by American Physiological Society
A thermodynamic model of hemoglobin suitable for physiological applications
T. Yoshida and M. Dembo
Isotope and Structural Chemistry, Group INC-4, Los Alamos National Laboratory, New Mexico 87545.
We propose a quantitative model of the thermodynamics of hemoglobin in
contact with its five major ligands (O2, CO2, Cl-, 2,3-bisphosphoglycerate,
and H+). Our model incorporates the two-state formalism of J. Monod, J.
Wyman, and J.P. Changeux (J. Mol. Biol. 12: 88-118, 1965) for treatment of
quanternary transitions and also the mean field formalism of K.
Linderstrom-Lang (C. R. Trav. Lab. Carlsberg Ser. Chim. 15: 1-30, 1924) for
treatment of electrostatic interactions. On the basis of this approach, we
develop an algorithm for the efficient computation of observable
quantities, such as the occupancy of various ligand binding sites, and an
objective statistical procedure for determining both maximum likelihood
values and confidence limits of all the intrinsic thermodynamic parameters
of hemoglobin. Finally, we show that the predictions of our theory are in
good agreement with independent experimental observations.
