showing 3 related works from this author
A molecular dynamics study on the role of the protonation state in the biosynthesis of R-PAC by AHAS
2019
Abstract The effect of the protonation state of the hydroxyl-ethylthiamin diphosphate intermediate, HEThDP, on the enzyme-substrate interactions and their consequences on the biosynthesis of R-phenylacetylcarbinol, R-PAC, by the acetohydroxy acid synthase, AHAS, is addressed by molecular dynamics simulations. It is found that the form of HEThDP, which favors the formation of R-PAC, is that having the 4-aminopyrimidine ring with the N1′ atom protonated and the N4′ atom as aminopyrimidinium ion. Under this form both active sites of AHAS have the ability to perform the catalysis, unlike that observed for the other possible protonation states of N1′ and N4′ atoms.
A DFT study on the chiral synthesis of R-phenylacetyl carbinol within the quantum chemical cluster approach
2017
Abstract The reaction pathway leading to R-phenylacetyl carbinol within the quantum chemical cluster approach is addressed by means of density functional theory (DFT) calculations. The study includes calculation of Fukui functions, activation free energies, and potential energy surface scans, both in gas and solution phase. The protonation states of the nitrogen atoms of the pyrimidine moiety are determined. The reaction appears to be slightly exergonic (ΔG 0 = −5.6 and −4.0 kcal/mol for gas and solution phase, respectively) following a concerted synchronous mechanism having activation free energy barriers of 16.2 and 13.3 kcal/mol, in gas phase and solution phase, respectively.
Mechanistic study of the biosynthesis of R-phenylcarbinol by acetohydroxyacid synthase enzyme using hybrid quantum mechanics/molecular mechanics simu…
2021
Abstract The biosynthesis of R-phenylacetylcarbinol (R-PAC) by the acetohydroxy acid synthase, (AHAS) is addressed by molecular dynamics simulations (MD), hybrid quantum mechanics/molecular mechanics (QM/MM), and QM/MM free energy calculations. The results show the reaction starts with the nucleophilic attack of the C2α atom of the HEThDP intermediate on the Cβ atom of the carbonyl group of benzaldehyde substrate via the formation of a transition state (TS1) with the HEThDP intermediate under 4′-aminopyrimidium (APH+) form. The calculated activation free energy for this step is 17.4 kcal mol−1 at 27 °C. From this point, the reaction continues with the abstraction of Hβ atom of the HEThDP in…