A quantitative model for oxygen uptake and release in a family of hemeproteins

J.P. BUSTAMANTE; M.E. SZRETTER; M. SUED; M.A. MARTI; D.A. ESTRIN; L. BOECHI

BIOINFORMATICS (OXFORD, ENGLAND)

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2016 vol. 32 p. 1805 - 1813

1367-4803

Hemeproteins have many diverse functions that largely depend on the rate at whichthey uptake or release small ligands, like oxygen. These proteins have been extensively studiedusing either simulations or experiments, albeit only qualitatively and one or two proteins at a time.Results: We present a physical?chemical model, which uses data obtained exclusively from com-puter simulations, to describe the uptake and release of oxygen in a family of hemeproteins, calledtruncated hemoglobins (trHbs). Through a rigorous statistical analysis we demonstrate that ourmodel successfully recaptures all the reported experimental oxygen association and dissociationkinetic rate constants, thus allowing us to establish the key factors that determine the rates at whichthese hemeproteins uptake and release oxygen. We found that internal tunnels as well as the distalsite water molecules control ligand uptake, whereas oxygen stabilization by distal site residuescontrols ligand release. Because these rates largely determine the functions of these hemeproteins,these approaches will also be important tools in characterizing the trHbs members with unknownfunctions.