title: Theoretical modeling of enzyme reactions: the thermodynamics of formation of compound 0 in horseradish peroxidase.
abstract: 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.
authors.affiliation: Consorzio Interuniversitario per le Applicazioni di Supercalcolo per Università e Ricerca (CASPUR), Via dei Tizii 6b, Rome, Italy.
authors.forename: Costantino
authors.initials: C
authors.lastname: Zazza
authors.forename: Andrea
authors.initials: A
authors.lastname: Amadei
authors.forename: Amedeo
authors.initials: A
authors.lastname: Palma
authors.forename: Nico
authors.initials: N
authors.lastname: Sanna
authors.forename: Simone
authors.initials: S
authors.lastname: Tatoli
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Aschi
mesh_terms: D003198:Computer Simulation; D006735:Horseradish Peroxidase / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure; D013816:Thermodynamics
chemical_list: D006735:Horseradish Peroxidase