A quantum-chemical picture of hemoglobin affinity.

ABSTRACT: Understanding the molecular mechanism of hemoglobin cooperativity remains an enduring challenge. Protein forces that control ligand affinity are not directly accessible by experiment. We demonstrate that computational quantum mechanics/molecular mechanics methods can provide reasonable values of ligand binding energies in Hb, and of their dependence on allostery. About 40% of the binding energy differences between the relaxed state and tense state quaternary structures result from strain induced in the heme and its ligands, especially in one of the pyrrole rings. The proximal histidine also contributes significantly, in particular, in the alpha-chains. The remaining energy difference resides in protein contacts, involving residues responsible for locking the quaternary changes. In the alph

SUBMITTER: Alcantara RE 

PROVIDER: S-EPMC2141797 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature