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

SUED, MARIELA; BOECHI, LEONARDO; SZRETTER, MARÍA EUGENIA; ESTRÍN, DARÍO A.; BUSTAMANTE, JUAN PABLO; MARTÍ, MARCELO A.

BIOINFORMATICS (OXFORD, ENGLAND)

OXFORD UNIV PRESS

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

1367-4803

Motivation: Hemeproteins have many diverse functions that largelydepend on the rate at which they uptake or release small ligands, likeoxygen. These proteins have been extensively studied using eithersimulations or experiments, albeit only qualitatively and one or twoproteins at a time.Results: We present a physical-chemical model, which uses dataobtained exclusively from classical molecular dynamics simulations,to describe the uptake and release of oxygen in a family ofhemeproteins, called truncated hemoglobins. Through a rigorousstatistical analysis we demonstrate that our model successfullyrecaptures all the reported experimental oxygen association anddissociation kinetic rate constants, thus allowing us to establish thekey factors that determine the rates at which these hemeproteinsuptake and release oxygen. We found that internal tunnels as well asthe distal site water molecules control ligand uptake, whereas oxygenstabilization by distal site residues controls ligand release.Because these rates largely determine the functions of thesehemeproteins, these approaches will also be important tools incharacterizing the truncated hemoglobins members with unknownfunctions.Contact: lboechi@ic.fcen.uba.ar