A quantitative model for oxygen uptake and release in hemeproteins

BUSTAMANTE, JUAN PABLO; SZRETTER, MARÍA EUGENIA; SUED, MARIELA; MARTÍ, MARCELO; ESTRIN, DARÍO; BOECHI, LEONARDO

Salto

Congreso; Latin American Conference on Mathematical Modeling of Biological Systems; 2015

Small ligand affinity is determined by the ratio between the association (kon) and dissociation (koff) rate constants, which characterize the corresponding processes. Both kinetic rate constants measurements are among the most useful methods to address the moieties controlling ligand entry and exit in proteins. We present a physical-chemical model, which uses data obtained exclusively from single-molecule computer simulations, i.e. atomistic descriptions of the evolution of a protein structure over time immersed in an aqueous solvent, to describe the uptake and release of oxygen in hemeproteins. Through a rigorous statistical analysis we demonstrate that this model successfully recaptures all the reported association and dissociation rate constants. We are thus able to identify the key factors that regulate the oxygen uptake and release in these proteins. We also propose different approaches to quantitatively estimate the kinetic rate constants for the rest of the unknown hemeproteins structures.