QM/MM Study of a Nucleophilic Substitution Reaction Catalyzed by Uridine Phosphorylase from Vibrio cholerae
Abstract
:1. Introduction
2. Materials and Methods
2.1. Preparation and Parameterization
2.2. Levels of Theory Used
2.3. Calculations of the Reaction Path and the Transition State
2.4. Calculations of Thermochemical Parameters
2.5. Calculations for the Nucleophilic Attack Reaction without an Enzyme
3. Results and Discussion
3.1. Optimized Structures of Substrate Complexes and Products with UP
3.2. Reaction Pathway and Transition State for the Nucleophilic Attack of Hydrogen Phosphate Ion on Uridine
3.3. Nucleophilic Substitution Reaction Involving Hydrogen Orthovanadat Anion
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
QM/MM | Quantum Mechanics/Molecular Modelling |
UP | Uridine Phosphorylase |
aa | amino acid residues |
xTB | extended Tight-binding method |
DFT | Density Functional Theory |
MEP | Minimum Energy Path |
NEB-CI | Climbing Image Nudged Elastic Band method |
EF | Eigenvector Following method |
IDPP | Image-Dependent-Pair-Potential method |
PHVA | Partial Hessian |
qRRHO | quasi-Rigid Rotor Harmonic Oscillator |
URA | Uracil moiety |
RIB | Ribosyl moiety |
PME | Particle-Mesh Evald method |
DPLNO | Domain-based Local Pair Natural Orbital computational scheme |
CCSD(T) | Coupled Cluster Single-Double-Triple method |
SCF | Self-Consistent Field |
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Calculation Methods | ER (s/e) | EA (s/e) | ER (DFT) | EA (DFT) | ER (CC) | EA (CC) | GR (CC) | GA (CC) |
---|---|---|---|---|---|---|---|---|
XTB-GFN2 (MEP 1, OPT 2, FREQ 3) | −2.6 | 31.2 | 3.3 | 13.4 | 1.9 | 20.2 | 3.6 | 17.7 |
XTB-GFN2 (MEP, FREQ) + B3LYP 4 (OPT) | −1.0 | 32.0 | 1.5 | 10.5 | 0.2 | 16.6 | 0.6 | 14.0 |
B3LYP (MEP, OPT) + XTB-GFN2(FREQ) | −1.0 | 32.5 | 1.5 | 10.6 | 0.2 | 16.7 | 0.6 | 14.0 |
B97-3c | - | - | −1.2 | 9.1 | 0.2 | 16.4 | 0.1 | 14.7 |
Solvent (water, C-PCM) w/o enzime | ||||||||
B3LYP | - | - | 10.7 | 33.6 | 9.0 | 38.4 | 6.8 | 35.3 |
B3LYP, each reactant/product separately | - | - | −3.4 | 13.8 | −3.4 | 21.5 | −2.6 | 35.6 |
B97-3c | - | - | 7.9 | 24.8 | 8.6 | 34.4 | 8.0 | 31.6 |
B97-3c, each reactant/product separately | - | - | - | - | −8.3 | 13.0 | −7.5 | 26.5 |
Nucleophilic substitution reaction involving hydroorthovanadat-ion | ||||||||
B97-3c | - | - | −6.1 | 7.3 | −3.8 | 14.4 | −3.7 | 12.6 |
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Lashkov, A.A.; Eistrich-Geller, P.A.; Samygina, V.R.; Rubinsky, S.V. QM/MM Study of a Nucleophilic Substitution Reaction Catalyzed by Uridine Phosphorylase from Vibrio cholerae. Crystals 2023, 13, 803. https://doi.org/10.3390/cryst13050803
Lashkov AA, Eistrich-Geller PA, Samygina VR, Rubinsky SV. QM/MM Study of a Nucleophilic Substitution Reaction Catalyzed by Uridine Phosphorylase from Vibrio cholerae. Crystals. 2023; 13(5):803. https://doi.org/10.3390/cryst13050803
Chicago/Turabian StyleLashkov, Alexander A., Polina A. Eistrich-Geller, Valeriya R. Samygina, and Sergey V. Rubinsky. 2023. "QM/MM Study of a Nucleophilic Substitution Reaction Catalyzed by Uridine Phosphorylase from Vibrio cholerae" Crystals 13, no. 5: 803. https://doi.org/10.3390/cryst13050803
APA StyleLashkov, A. A., Eistrich-Geller, P. A., Samygina, V. R., & Rubinsky, S. V. (2023). QM/MM Study of a Nucleophilic Substitution Reaction Catalyzed by Uridine Phosphorylase from Vibrio cholerae. Crystals, 13(5), 803. https://doi.org/10.3390/cryst13050803