Free-Energy Profile for CO Binding to Separated Chains of Human andTrematomus newnesi Hemoglobin: Insights from Molecular Dynamics Simulations and Perturbed Matrix Method

Antonello Merlino*†‡, Alessandro Vergara†‡, Filomena Sica†‡, Massimiliano Aschi§, Andrea Amadei, Alfredo Di Nola and Lelio Mazzarella†‡
Dipartimento di Chimica, University of Naples “Federico II”, Complesso Universitario Monte S. Angelo, Via Cinthia, I-80126 Naples, Italy, Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, I-80134 Naples, Italy, Dipartimento di Chimica, Ingegneria Chimica e Materiali, University of L’Aquila, Via Vetoio, I-67010, L’Aquila, Italy, Dipartimento di Scienze e Tecnologie Chimiche, University of Rome “Tor Vergata”, Via della Ricerca scientifica 1, I-00133 Roma, Italy, and Dipartimento di Chimica, University of Rome “La Sapienza”, P.le Aldo Moro 5, I-00185 Roma, Italy
J. Phys. Chem. B, 2010, 114 (20), pp 7002–7008
DOI: 10.1021/jp908525s
Publication Date (Web): April 30, 2010
Copyright © 2010 American Chemical Society
* To whom correspondence should be addressed. Fax: +39081 674090. Tel.: +39081 674276. E-mail:antonello.merlino@unina.it., † 

University of Naples “Federico II”.

 

 

FULL TEXT

Abstract

 

The free-energy profile and the classical kinetics of the heme carbomonoxide binding−unbinding reaction have been derived by means of a theoretical method for the separated chains of human (HbA) and Trematomus newnesi major component (HbTn) hemoglobin. The results reveal that the α- and β-chains of HbA have similar values of kinetic constants for the dissociation of the Fe−CO state, in agreement with experimental data. Comparisons of the present findings with the data obtained for the α- and β-chains of HbTn and with theoretical and experimental results previously collected on myoglobin provide a detailed picture of this important biochemical reaction in globins. The sequence and structural differences among the globins are not reflected in meaningful variations in the rate of CO dissociation. These data support the conclusion that the differences observed for the reaction with CO of globins, if any, involve the rate of ligand migration to the solvent, rather than the Fe−CO complex formation/rupture. Furthermore, our results agree with the recent discovery that globin family proteins exhibit common dynamics, thus confirming the observation that the dynamic properties of proteins are strongly related to their overall architecture.