On the catalytic role of structural fluctuations in enzyme reactions: computational evidence on the formation of compound 0 in horseradish peroxidase

Zazza, Costantino; Palma, Amedeo; Amadei, Andrea; Sanna, Nico; Tatoli, Simone; Aschi, Massimiliano

doi:10.1039/b906614d

Cited by 5 publications

(10 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…the Perturbed Matrix Method (PMM), [19][20][21] constructed within a basic statistical-mechanical formulation, repeatedly showed to be able to provide a valid complementary viewpoint to the more popular Quantum Mechanics/Molecular Mechanics (QM/MM) 22,23 approaches, for modelling several chemical processes both in dilute solution 24,25 and in protein. [26][27][28][29] As a natural consequence of our efforts in this direction ET reactions represent a crucial step and, although in some of our previous studies examples of charge-transfer processes have been encountered and investigated, 26,30,31 a systematic and general PMM-based approach is still missing.…”

Section: Introductionmentioning

confidence: 99%

A general theoretical model for electron transfer reactions in complex systems

Amadei

Daidone

Aschi

2012

Phys. Chem. Chem. Phys.

Self Cite

View full text Add to dashboard Cite

In this paper we present a general theoretical-computational model for treating electron transfer reactions in complex atomic-molecular systems. The underlying idea of the approach, based on unbiased first-principles calculations at the atomistic level, utilizes the definition and the construction of the Diabatic Perturbed states of the involved reactive partners (i.e. the quantum centres in our perturbation approach) as provided by the interaction with their environment, including their mutual interaction. In this way we reconstruct the true Adiabatic states of the reactive partners characterizing the electron transfer process as the fluctuation of the electronic density due to the fluctuating perturbation. Results obtained by using a combination of Molecular Dynamics simulation and the Perturbed Matrix Method on a prototypical intramolecular electron transfer (from 2-(9,9'-dimethyl)fluorene to the 2-naphthalene group separated by a steroidal 5-α-androstane skeleton) well illustrate the accuracy of the method in reproducing both the thermodynamics and the kinetics of the process.

show abstract

Section: Introductionmentioning

confidence: 99%

A general theoretical model for electron transfer reactions in complex systems

Amadei

Daidone

Aschi

2012

Phys. Chem. Chem. Phys.

Self Cite

View full text Add to dashboard Cite

show abstract

“…[2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Whereas DFT is appropriate for model systems, the enzymatic species require a combined quantum mechanical/molecular mechanical (QM/MM) approach, [19][20][21][22][23][24][25][26][27][28][29] using DFT as the QM method for describing the active species and MM force fields to account as realistically as possible for the effect of protein environment. Indeed, QM(DFT)/MM studies have appeared by now for many heme proteins, e.g., cytochrome P450, 30 cytochrome c peroxidase (CcP) and ascorbate peroxidase (APX), [31][32][33][34][35] catalase and catalase-peroxidase, [36][37][38][39] horseradish peroxidase (HRP), [40][41][42][43][44][45][46][47] nitric oxide synthase (NOS), [48][49]…”

Section: Introductionmentioning

confidence: 99%

“…Until now, density functional theory (DFT) has played the dominant role in the interplay of theoretical and experimental efforts toward achieving this requisite understanding of the chemistry of heme species. − Whereas DFT is appropriate for model systems, the enzymatic species require a combined quantum mechanical/molecular mechanical (QM/MM) approach, − using DFT as the QM method for describing the active species and MM force fields to account as realistically as possible for the effect of protein environment. Indeed, QM(DFT)/MM studies have appeared by now for many heme proteins, e.g., cytochrome P450, cytochrome c peroxidase (C c P) and ascorbate peroxidase (APX), − catalase and catalase-peroxidase, − horseradish peroxidase (HRP), − nitric oxide synthase (NOS), − heme oxygenase (HO), , myoglobin (Mb) and hemoglobin (Hb), − truncated Hb, − chloroperoxidase (CPO), − and tryptophan/indoleamine 2,3-dioxygenase (TDO/IDO). − …”

Section: Introductionmentioning

confidence: 99%

Multireference and Multiconfiguration Ab Initio Methods in Heme-Related Systems: What Have We Learned So Far?

2011

View full text Add to dashboard Cite

This work reviews the recent applications of ab initio multireference/multiconfiguration (MR/MC) electronic structure methods to heme-related systems, involving tetra-, penta-, and hexa-coordinate species, as well as the high-valent iron-oxo species. The current accuracy of these methods in the various systems is discussed, with special attention to potential sources of systematic errors. Thus, the review summarizes and tries to rationalize the key elements of MR/MC calculations, namely, the choice of the employed active space, especially the so-called double-shell effect that has already been recognized to be important in transition-metal-containing systems, and the impact of these elements on the spin-state energetics of heme species, as well as on the bonding mechanism of small molecules to the heme. It is shown that expansion of the MC wave function into one based on localized orbitals provides a compact and insightful view on some otherwise complex electronic structures. The effects of protein environment on the MR/MC results are summarized for the few available quantum mechanical/molecular mechanical (QM/MM) studies. Comparisons with corresponding DFT results are also made wherever available. Potential future directions are proposed.

show abstract

“…15 In this respect, we have applied the perturbed matrix method (PMM) computational procedure, successfully used to evaluate solvent effects on electronic properties of organic molecules in complex atomistic environment at room temperature. [19][20][21][22][23] Interestingly, the currently proposed PMM(TD-DFT/MD) approach, carried out considering the TPT drug [IUPAC name: (S)-10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3′,4′:6,7]in- dolizino [1,2-b] quinoline-3,14(4H,12H)-dione monohydrochloride)] in water solution, provides UV-vis spectroscopic properties, which are found to be in agreement with experimental absorption bands at moderately acidic conditions 15 and with high-level CPCM-based computations also in the presence of explicit solvent water molecules at the solute-solvent interface. Such a result unequivocally demonstrates that the UV-vis spectrum at pH ) 6.8 of the TPT drug in liquid water is due to the contribution of T2A and T2B structural isomers (see Figure 1a).…”

Section: Introductionmentioning

confidence: 99%

Solvent Effects on the Valence UV−Vis Absorption Spectra of Topotecan Anticancer Drug in Aqueous Solution at Room Temperature: A Nanoseconds Time-Scale TD-DFT/MD Computational Study

et al. 2010

Self Cite

View full text Add to dashboard Cite

The low-lying valence electronic excitations of the topotecan anticancer drug, in two stable lactone forms, have been addressed in infinite dilute aqueous solution by combining time-dependent density functional theory calculations with nanoseconds time-scale classical molecular dynamics simulations at 298 K. The effects of the surrounding and fluctuating classical environment on the investigated topotecan forms are included in a perturbed electronic Hamiltonian, which is computed, and then diagonalized, at each frame stored during the molecular dynamics sampling in explicit solution. Current results clearly indicate that, at moderately acidic and physiological conditions, the valence UV-vis absorption spectra of topotecan drug are strongly affected by the surrounding dielectric media and by its perturbing trajectory as arising from finite-temperature fluctuations and supramolecular interactions. Furthermore, the extension of the proposed computational study to hydrated topotecan complexes in liquid water shows that all of the experimentally detected UV-vis spectroscopic features in solution are accurately reproduced only when direct solute-solvent intermolecular interactions are also explicitly taken into account in our simulating scenario. Finally, the present investigation opens up a chance regarding the computational prediction of the UV-vis absorption spectra of topotecan interacting, in silico, with the topoisomerase-DNA binary complex in physiological conditions (i.e., water dilute solution, room temperature).

show abstract

On the catalytic role of structural fluctuations in enzyme reactions: computational evidence on the formation of compound 0 in horseradish peroxidase

Abstract: Interplay of theory and computation in chemistryexamples from on-water organic catalysis, enzyme catalysis, and single-molecule fluctuations

Cited by 5 publications

References 37 publications

A general theoretical model for electron transfer reactions in complex systems

A general theoretical model for electron transfer reactions in complex systems

Multireference and Multiconfiguration Ab Initio Methods in Heme-Related Systems: What Have We Learned So Far?

Solvent Effects on the Valence UV−Vis Absorption Spectra of Topotecan Anticancer Drug in Aqueous Solution at Room Temperature: A Nanoseconds Time-Scale TD-DFT/MD Computational Study

Contact Info

Product

Resources

About