Allosteric signalling paths in hemoglobin: a protein dynamics network analysis

Abstract Hemoglobin is the paradigm of cooperative protein-ligand binding. Cooperativity is the consequence of inter-subunit allosteric communication: binding at one site increases the affinity of the others. Despite half a century of studies, the mechanism behind oxygen binding in hemoglobin is not fully understood yet. In particular, it is not clear if cooperativity arises from preferential inter-subunit channels and which residues propagate the allosteric signal from one heme to the others. In this work, the heme-heme dynamical interactions have been mapped through a network-based analysis of residue conformational fluctuations, as described by molecular dynamics simulations. In particular, it was possible to suggest which inter-subunit interactions are mostly responsible of allosteric signalling and, within each pair of subunits, which protein fragments convey such signalling process.