We report two new analytical fits of the ground potential energy surface ͑PES͒ ( 2 AЈ) and the first excited PES ( 4 AЈ) involved into the title reaction and its reverse, using ab initio electronic structure calculations from Papers I and II along with new grids of ab initio points by means of the second-order perturbation theory on CASSCF wave function ͓CASPT2 ͑17,12͒ G2/aug-cc-pVTZ͔ reported here ͑1250 points for the 2 AЈ PES and 910 points for the 4 AЈ PES͒. Some experimental data were also introduced to better account for the exoergicity and the experimental rate constant at 300 K. The final root-mean-square deviations of the fits were 1.06 and 1.67 kcal/mol for 2 AЈ and the 4 AЈ PESs, respectively, for the NOO C s abstraction and insertion regions of the PESs. Thermal rate constants were calculated ͑300-5000 K͒ for both the direct and reverse reactions by means of the variational transition state theory with the inclusion of a microcanonical optimized multidimensional tunneling correction, obtaining a very good agreement with the experimental data within all the temperature range. The new analytical 2 AЈ PES presents several stationary points not introduced in previous analytical surfaces, and describes accurately the NO 2 (X 2 A 1 ) minimum, which seems to be very accessible according to the trajectories run in a preliminary quasiclassical trajectory study. The new analytical 4 AЈ PES has a lower energy barrier than the previous one, which increases significantly the contribution of this PES to the total rate constant at high temperatures. Moreover, the new analytical PESs not only describe accurately the C s regions of the NOO system but also the ONO C 2v or near C 2v regions.

The link atom (LA) and the generalized hybrid orbital (GHO) quantum mechanical/molecular mechanics (QM/MM) boundary treatment methods are compared, in the context of the acylation process (the rate-limiting step) involving the NS3/NS4A HCV serine protease and its NS5A/5B natural substrate. The potential energy surface was calculated, and the free energy along the selected reaction coordinate was obtained from umbrella sampling molecular dynamics simulations, at the AM1/CHARMM27 level. The LA and GHO methods, when properly applied, lead to similar chemical behavior, although the agreement is not quantitative. The choice of QM/MM partitioning is dictated to some extent by the nature of the two different methods, and this influences the results. The free energy profiles obtained by umbrella sampling suggest that the GHO approach is better suited for this system, because it provides a consistent description of the reaction in both the forward and backward directions. This is probably a consequence of the different QM/MM partitioning required by the two different methods (i.e., different numbers of atoms have to be included in the QM region). This finding is therefore likely to be system dependent, so careful testing should be considered for each enzyme application.

Articles you may be interested inCommunication: Rigorous quantum dynamics of O + O2 exchange reactions on an ab initio potential energy surface substantiate the negative temperature dependence of rate coefficients Kinetic and dynamic studies of the Cl(2 P u) + H2O( X ̃ 1 A 1) → HCl( X ̃ 1Σ+) + OH( X ̃ 2Π) reaction on an ab initio based full-dimensional global potential energy surface of the ground electronic state of ClH2O J. Chem. Phys. 139, 074302 (2013); 10.1063/1.4817967 N(4 S/2 D)+N2: Accurate ab initio-based DMBE potential energy surfaces and surface-hopping dynamics J. Chem. Phys. 137, 22A515 (2012); 10.1063/1.4737858 Ab initio ground potential energy surface and quasiclassical trajectory study of the O ( 1 D)+ CH 4 (X 1 A 1 )→ OH (X 2 Π)+ CH 3 (X 2 A 2 ″ ) reaction dynamics J. Chem. Phys. 111, 8913 (1999); 10.1063/1.480236Ab initio ground potential energy surface, VTST and QCT study of the O ( 3 P)+ CH 4 (X 1 A 1 )→ OH (X 2 Π)+ CH 3 (X 2 A 2 ″ ) reaction

Articles you may be interested inQuantum real wave-packet dynamics of the N ( S 4 ) + N O ( X ̃ Π 2 ) → N 2 ( X ̃ Σ g + 1 ) + O ( P 3 ) reaction on the ground and first excited triplet potential energy surfaces: Rate constants, cross sections, and product distributions Ab initio derived analytical fits of the two lowest triplet potential energy surfaces and theoretical rate constants for the N ( 4 S)+ NO (X 2 Π) system Quantum reactive scattering calculations of cross sections and rate constants for the N ( 2 D)+ O 2 (X 3 Σ g − )→ O ( 3 P)+ NO (X 2 Π) reactionWe report real wave packet ͑WP͒ calculations of reaction probabilities, cross sections, rate constants, and product distributions of the reaction N( 4 S)ϩO 2 (X 3 ͚ g Ϫ )→NO(X 2 ͟)ϩO( 3 P). We propagate initial WPs corresponding to several O 2 levels, and employ reactant coordinates and a flux method for calculating initial-state-resolved observables, or product coordinates and an asymptotic analysis for calculating state-to-state quantities. Exact or J-shifting calculations are carried out at total angular momentum Jϭ0 or JϾ0, respectively. We employ the recent X 2 AЈ S3 potential energy surface ͑PES͒ by Sayós et al. and the earlier a 4 AЈ PES by Duff et al. In comparing S3 results with the WP ones of a previous X 2 AЈ S2 PES, we find lower S3 energy thresholds and larger S3 probabilities, despite the higher S3 barrier. This finding is due to the different features of the doublet PESs in the reactant and product channels, at the transition state, and in the NO 2 equilibrium region. We analyze the effects of the O 2 initial level and show that tunneling through the S3 barrier enhance the room-temperature rate constant by ϳ3.7 times with respect to the previous S2 WP rate. The agreement with the room-temperature experimental result is thus notably improved. The NO vibrational distribution is inverted and the rotational ones are strongly oscillating. We explain these nonstatistical results showing that the reaction partners approach each other with a large impact parameter. The WP vibrational distribution is however different from that observed, which is oscillating. WP calculations show that the new S3 PES describes accurately several features of the X 2 AЈ state, although a lowering of its barrier height by ϳ0.56 kcal/mol should bring calculated and observed rate constants in full agreement.

Combined quantum mechanics and molecular mechanics (QM/MM) calculations were carried out to characterize the reaction mechanism of the NS3 protease with its preferred substrate (NS5A/5B). The main purpose of this study was to locate the barrier states and intermediates along the distinguished coordinate path (DCP) involved in this process. These structures, and in particular the one corresponding to the first barrier state and intermediate (B1 and I1), could be a starting point for the synthesis of inhibitors of this protease, which could be used to treat hepatitis C. The two first steps of the reaction mechanism were studied, i.e., the acylation step and the breaking of the peptide bond. The first step takes place through a tetracoordinated intermediate, as suggested from previous works on other Serine proteases. The importance of the different amino acid residues was also considered (perturbation study where the MM charges of each residue were set to zero independently). The residues of the oxyanion hole were confirmed as the most important for the electrostatic stabilization of the tetracoordinate intermediate. Moreover, the role of other residues, e.g., Arg-155 and Asp-79, was also explained.