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The reaction mechanism of paraoxon hydrolysis by phosphotriesterase from combined QM/MM simulations.
A dual-level QM/MM approach is used that synthesizes accurate results from high-level electronic structure calculations with computational efficiency of semiempirical QM /MM potentials for free energy simulations to suggest a revised mechanism for the phosphotriester hydrolysis mechanism by PTE.
Experimental and computational analysis of the transition state for ribonuclease A-catalyzed RNA 2′-O-transphosphorylation
- H. Gu, Shuming Zhang, M. Harris
- Chemistry, BiologyProceedings of the National Academy of Sciences
- 22 July 2013
The ability to obtain a chemically detailed description of 2′-O-transphosphorylation transition states provides an opportunity to advance understanding of biological catalysis significantly by determining how the catalytic modes and active site environments of phosphoryl transferases influence transition state structure.
Characterization of the reaction path and transition states for RNA transphosphorylation models from theory and experiment.
- K. Wong, H. Gu, Shuming Zhang, J. Piccirilli, M. Harris, D. York
- ChemistryAngewandte Chemie
- 16 January 2012
Experimental and computational results are presented to characterize the mechanism of model phosphoryl transfer reactions that mimic RNA cleavage transesterification catalyzed by enzymes such as RNase A as well as endonucleolytic ribozymes such as the hammerhead, hairpin, hepatitis delta virus, VS and glmS RNAozymes.
Active participation of Mg ion in the reaction coordinate of RNA self-cleavage catalyzed by the hammerhead ribozyme.
Results support the plausibility of a cleavage mechanism where phosphoryl transfer and general acid catalysis are stepwise, and where the catalyt...
Combined QM/MM and path integral simulations of kinetic isotope effects in the proton transfer reaction between nitroethane and acetate ion in water
It is found that the mixed isotopic Swain–Schaad exponents are very close to the semiclassical limits, suggesting that tunneling effects do not significantly affect this property for the reaction between nitroethane and acetate ion in aqueous solution.
Roadmaps through free energy landscapes calculated using the multi-dimensional vFEP approach.
- Tai-Sung Lee, B. Radak, Ming Huang, K. Wong, D. York
- ChemistryJournal of chemical theory and computation
- 14 January 2014
The proposed 2D-vFEP approach effectively addresses the two major obstacles to constructing free energy profiles from simulation data using traditional methods: the need for overlap in the re-weighting procedure and the problem of data representation.
Mechanistic insights into RNA transphosphorylation from kinetic isotope effects and linear free energy relationships of model reactions.
- Haoyuan Chen, T. Giese, M. Huang, K. Wong, M. Harris, D. York
- Chemistry, BiologyChemistry
- 27 October 2014
Density-functional calculations are applied to determine KIEs for a series of phosphoryl transfer reactions of direct relevance to the 2'-O-transphosphorylation that leads to cleavage of the phosphodiester backbone of RNA, demonstrating the utility of building up knowledge of mechanism through the systematic study of model systems to provide insight into more complex biological systems such as phosphoryL transfer enzymes and ribozymes.
Determination of the structure form of the fourth ligand of zinc in Acutolysin A using combined quantum mechanical and molecular mechanical simulation.
- E. Wu, K. Wong, Xin Zhang, Keli Han, Jiali Gao
- ChemistryThe journal of physical chemistry. B
- 26 February 2009
The theoretical results indicate that the fourth ligand in the active site of the reported X-ray crystal structure is a water molecule rather than a hydroxide anion, which can be attributed to the deprotonation of the zinc-bound water to yield a better nucleophile, the hydroxides ion.
Exact Relation between Potential of Mean Force and Free-Energy Profile.
New, general, exact relations between potential of mean force and free-energy profile are derived and it is revealed that in addition to the Jacobian determinant, theJacobian scale factor and Leibnizian contributions must also be considered.