Theoretical modeling of enzyme reactions: the thermodynamics of formation of compound 0 in horseradish peroxidase.
In this paper, by using the perturbed matrix method (PMM) in combination with basic statistical mechanical relations both based on nanosecond time-scale molecular dynamics (MD) simulations, we quantitatively address the thermodynamics of compound 0 (Cpd 0) formation in horseradish peroxidase (HRP) enzyme. Our results, in the same trend of low-temperature experimental data, obtained in cryoenzymology studies indicate that such a reaction can be described essentially as a stepwise spontaneous process: a first step mechanically constrained, strongly exothermic proton transfer from the heme-H2O2 complex to the conserved His42, followed by a solvent-protein relaxation involving a large entropy increase. Critical evaluation of PMM/MD data also reveals the crucial role played by specific residues in the reaction pocket and, more in general, by the conformational fluctuations of the overall environment in physiological conditions.
Zazza
Costantino
C
Consorzio Interuniversitario per le Applicazioni di Supercalcolo per Università e Ricerca (CASPUR), Via dei Tizii 6b, Rome, Italy.
Amadei
Andrea
A
Palma
Amedeo
A
Sanna
Nico
N
Tatoli
Simone
S
Aschi
Massimiliano
M
D003198:Computer Simulation; D006735:Horseradish Peroxidase / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure; D013816:Thermodynamics
D006735:Horseradish Peroxidase