The concept of generalized enzyme reactions suggests that a wide variety of substrates can undergo enzymatic transformations,
including those whose biotransformation has not yet been realized. The use of quantum chemistry to evaluate kinetic feasibility
is an attractive approach to identify enzymes for the proposed transformation. However, the sheer number of novel transformations
that can be generated makes this impractical as a screening approach. Therefore, it is essential to develop structure/activity
relationships based on quantities that are more efficient to calculate. In this work, we propose a structure/activity relationship
based on the free energy of binding or reaction of non-native substrates to evaluate the catalysis relative to that of native
substrates. While Br?nsted-Evans-Polanyi (BEP) relationships such as that proposed here have found broad application in heterogeneous
catalysis, their extension to enzymatic catalysis is limited. We report here on density functional theory (DFT) studies for
C–C bond formation and C–C bond cleavage associated with the decarboxylation of six 2-keto acids by a thiamine-containing
enzyme (EC 1.2.7.1) and demonstrate a linear relationship between the free energy of reaction and the activation barrier.
We then applied this relationship to predict the activation barriers of 17 chemically similar novel reactions. These calculations
reveal that there is a clear correlation between the free energy of formation of the transition state and the free energy
of the reaction, suggesting that this method can be further extended to predict the kinetics of novel reactions through our
computational framework for discovery of novel biochemical transformations. 相似文献
Infrared (IR) and vibrational circular dichroism (VCD) spectra of chiral camphor, camphorquinone and camphor-10-sulfonic acid (CSA), known as standard compounds for electronic circular dichroism (ECD) spectroscopy, are measured and their vibrational frequencies, infrared intensities, and rotational strengths are calculated using density functional theory (DFT). The observed IR and VCD spectra of chiral camphor and camphorquinone in carbon tetrachloride solution are reproduced by the DFT calculations, but those of CSA are not. DFT calculations of hydration models, where an anionic CSA specifically binds a few water molecules, are carried out. The average of the simulated VCD spectra in the hydration models is more consistent with the observed spectra. In addition, the wavelengths and dipole and rotational strengths for chiral camphor, camphorquinone, anionic CSA, and the hydration models were calculated by time-dependent DFT. In the region of 280-300 nm, the calculated wavelengths of the ECD bands for chiral camphor and camphorquinone coincide with the observed wavelengths that have been reported, and the calculated wavelengths for the hydration models are closer to the observed wavelengths reported than are those calculated for chiral anionic CSA. Consequently, the analysis combined with VCD and ECD spectroscopy using DFT calculations can elucidate the chirality of optically active molecules, even in an aqueous solution. 相似文献
Activated bleomycin (ABLM) is an oxygenated iron drug complex which embodies the drug's DNA-cleaving activity. This activity is exercised on DNA, if present, but if DNA is absent, the drug itself is inactivated. We have employed quantum density functional theory (DFT)-based methods to investigate (i) the structure of the Fe(II)BLM complex that is first formed in the human body after drug's administration, and (ii) the activation mechanism of the O–O bond present in the ABLM. We have identified the controversial second axial ligand as the endogenous oxygen atom of the carbamoyl group. Our first principles molecular dynamics (MD) simulations indicate a homolytic cleavage as the mechanism of the O–O bond activation in the ABLM complex. 相似文献
In this theoretical study we used density functional theory to calculate the molecular and crystalline structures of sodium
selenite. Our structural results were compared with experimental data. From the molecular structure we determined the ionization
potential, electronic affinity, and global reactivity parameters like electronegativity, hardness, softness and global electrophilic
index. A significant difference in the IP and EA values was observed, and this difference was dependent on the calculation
method used (employing either vertical or adiabatic energies). Thus, values obtained for the electrophilic index (2.186 eV
from vertical energies and 2.188 eV from adiabatic energies) were not significantly different. Selectivity was calculated
using the Fukui functions. Since the Mulliken charge study predicted a negative value, it is recommended that AIM should be
used in selectivity characterization. It was evident from the selectivity index that sodium atoms are the most sensitive sites
to nucleophilic attack. The results obtained in this work provide data that will aid the characterization of compounds used
in crop biofortification. 相似文献
Structures of model compounds mimicking aromatic amino acid residues in proteins are optimized by density functional theory (DFT), assuming that the main-chain conformation was a random coil. Excitation energies and dipole and rotational strengths for the optimized structures were calculated based on time-dependent DFT (TD-DFT). The electronic circular dichroism (ECD) bands of the models were significantly affected by side-chain conformations. Hydration models of the aromatic residues were also subjected to TD-DFT calculations, and the ECD bands of these models were found to be highly perturbed by the hydration of the main-chain amide groups. In addition to calculating the random-coil conformation, we also performed TD-DFT calculations of the aromatic residue models, assuming that the main-chain conformation was an alpha-helix or beta-strand. As expected, the overall feature of the ECD bands was also perturbed by the main-chain conformations. Moreover, vibrational circular dichroism (VCD) spectra of the hydration models in a random-coil structure were simulated by DFT, which showed that the VCD spectra are more sensitive to the side-chain conformations than the ECD spectra. The present results show that analyses combining ECD and VCD spectroscopy and using DFT calculations can elucidate the main- and side-chain conformations of aromatic residues in proteins. 相似文献
Monte Carlo track structure simulations were performed to investigate the effect of multiple ionization of water on the primary (or "escape") (at approximately 10(-6) s) yield of hydrogen peroxide (G(H2O2)) produced in the radiolysis of deaerated 0.4 M H2SO4 solutions by 12C6+ and 20Ne9+ ions at high linear energy transfer (LET) up to approximately 900 keV/microm. It was found that, upon incorporating the mechanisms of double, triple and quadruple ionizations of water in the calculations, a quantitative agreement between theory and experiment can be obtained. The curve for G(H2O2) as a function of LET reaches a well-defined maximum of approximately 1.4 molecules/100 eV at approximately 180-200 keV/microm, in very good accord with the available experimental data. Our results also show that, for the highest LET values considered in this study, the H2O2 escape yields obtained in 0.4 M sulfuric acid solutions are about 45% greater in magnitude than those found in neutral water. Contrary to a recent assumption suggesting that the limiting value of G(H2O2) at infinite LET should be approximately 1 molecule/100 eV, somewhat similar for neutral and acidic water, our simulations show a clear decrease in the primary H2O2 yields with increasing LET at high LET, indicating that the question of the limiting value of G(H2O2) at very high LET for both neutral and acidic liquid water is still open. 相似文献
The Fourier transform infrared (FT-IR) spectrum of 6-chloro-8-thia-1,4-epoxybicyclo[4.3.0]non-2-ene has been recorded in the region 4000–525 cm? 1. The optimised geometry, frequency and intensity of the vibrational bands of the title compound have been calculated using the ab initio Hartree–Fock and the density functional theory method with 6-31G(d,p) and 6-311G(d,p) basis set levels. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FT-IR spectrum. The observed and the calculated frequencies are found to be in good agreement. The theoretical vibrational spectrum of the title compound were interpreted by means of potential energy distributions using VEDA 4 program. 相似文献
Control of cytoplasmic pH (pHi) by a Na+/H+ antiport appears a general property of most eukaryotic cells. In human platelets activation of the Na+/H+ exchanger enhances Ca2+ mobilization and aggregation induced by low concentrations of thrombin (Siffert, W., and Akkerman, J. W. N. (1987) Nature 325, 456-458). Several observations indicate that the exchanger is regulated by protein kinase C. (i) Inhibitors of protein kinase C (trifluoperazine, sphingosine) inhibit the increase in pHi seen during thrombin stimulation as well as Ca2+ mobilization; artificially increasing pHi by monensin or NH4Cl then restores Ca2+ mobilization. (ii) Direct activation of protein kinase C by 1-oleoyl-2-acetylglycerol initiates an increase in pHi that depends on the presence of extracellular Na+ and is sensitive to inhibition by ethylisopropylamiloride. The pHi sensitivity of thrombin-induced Ca2+ mobilization is particularly evident in the range between pH 6.8 and 7.4 and at low thrombin concentrations, whereas thrombin concentrations of more than 0.2 unit/ml bypass the pH sensitivity. In the absence of thrombin an increase in pHi, either induced artificially (by addition of the ionophores nigericin or monensin) or via activation of protein kinase C (by addition of 1-oleoyl-2-acetylglycerol), does not induce Ca2+ mobilization. We conclude that activation of protein kinase C is essential for Ca2+ mobilization in platelets stimulated by low concentrations of thrombin and that protein kinase C exerts this effect via activation of the Na+/H+ exchanger. 相似文献
AbstractThe aptamers with the ability to form a G-quadruplex structure can be stable in the presence of some ions. Hence, study of the interactions between such aptamers and ions can be beneficial to determine the highest selective aptamer toward an ion. In this article, molecular dynamics (MD) simulations and quantum mechanics (QM) calculations have been applied to investigate the selectivity of the T30695 aptamer toward Pb2+ in comparison with some ions. The Free Energy Landscape (FEL) analysis indicates that Pb2+ has remained inside the aptamer during the MD simulation, while the other ions have left it. The Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) binding energies prove that the conformational stability of the aptamer is the highest in the presence of Pb2+. According to the compaction parameters, the greatest compressed ion-aptamer complex, and hence, the highest ion-aptamer interaction have been induced in the presence of Pb2+. The contact maps clarify the closer contacts between the nucleotides of the aptamer in the presence of Pb2+. The density functional theory (DFT) results show that Pb2+ forms the most stable complex with the aptamer, which is consistent with the MD results. The QM calculations reveal that the N-H bonds and the O…H distances are the longest and the shortest, respectively, in the presence of Pb2+. The obtained results verify that the strongest hydrogen bonds (HBs), and hence, the most compressed aptamer structure are induced by Pb2+. Besides, atoms in molecules (AIM) and natural bond orbital (NBO) analyses confirm the results.Communicated by Ramaswamy H. Sarma 相似文献
We have developed a Behler–Parrinello Neural Network (BPNN) that can be employed to calculate energies and forces of zirconia bulk structures with oxygen vacancies with similar accuracy as that of the density functional theory (DFT) calculations that were used to train the BPNN. In this work, we have trained the BPNN potential with a reference set of 2178 DFT calculations and validated it against a dataset of untrained data. We have shown that the bulk structural parameters, equation of states, oxygen vacancy formation energies and diffusion barriers predicted by the BPNN potential are in good agreement with the reference DFT data. The transferability of the BPNN potential has also been benchmarked with the prediction of structures that were not included in the reference set. The evaluation time of the BPNN is orders of magnitude less than corresponding DFT calculations, although the training process of the BPNN potential requires non-negligible amount of computational resources to prepare the dataset. The computational efficiency of the NN enabled it to be used in molecular dynamics simulations of the temperature-dependent diffusion of an oxygen vacancy and the corresponding diffusion activation energy. 相似文献
Genome sequences of cyanobacteria, Synechocystis sp. PCC 6803, Anabaena sp. PCC 7120, and Thermosynechococcus elongatus BP-1 revealed the presence of a single Ca2+/H+ antiporter in these organisms. Here, we isolated the putative Ca2+/H+ antiporter gene from Synechocystis sp. PCC 6803 (synCAX) as well as a homologous gene from a halotolerant cyanobacterium Aphanothece halophytica (apCAX). In contrast to plant vacuolar CAXs, the full-length apCAX and synCAX genes complemented the Ca2+-sensitive phenotype of an Escherichia coli mutant. ApCAX and SynCAX proteins catalyzed specifically the Ca2+/H+ exchange reaction at alkaline pH. Immunological analysis suggested their localization in plasma membranes. The Synechocystis sp. PCC 6803 cells disrupted of synCAX exhibited lower Ca2+ efflux activity and a salt-sensitive phenotype. Overexpression of ApCAX and SynCAX enhanced the salt tolerance of Synechococcus sp. PCC 7942 cells. Mutagenesis analyses indicate the importance of two conserved acidic amino acid residues, Glu-74 and Glu-324, in the transmembrane segments for the exchange activity. These results clearly indicate that cyanobacteria contain a Ca2+/H+ antiporter in their plasma membranes, which plays an important role for salt tolerance. 相似文献
Fourier transform infrared (FT-IR) and Fourier transform Raman (FT-Raman) spectra of 3,4-dihydroxy-l-phenylalanine (3,4-DPA) in solid phase were recorded and analysed in this research. Along with this, the IR spectra in CHCl3 and the use of acetone as solvents of 3,4-DPA were also recorded. The equilibrium geometry, bonding features and harmonic vibrational frequencies were investigated with the help of density functional theory (DFT) method. The 1H and 13C nuclear magnetic resonance chemical shifts of the molecule were calculated using the gauge including atomic orbital method and compared with experimental results. Stability of the molecule arising from hyperconjugative interactions and charge delocalisation was analysed using natural bond orbital analysis. The results show that charge in electron density (ED) in the σ* and π* antibonding orbitals and second-order delocalisation energies E(2) confirms the occurrence of intramolecular charge transfer within the molecule. UV–vis spectrum of the compound was recorded and the electronic properties, such as HOMO and LUMO energies, were analysed using the time-dependent (TD)-DFT approach. Finally, the calculation results were applied to simulate infrared and Raman spectra of the title compound, which showed good agreement with the observed spectra. 相似文献
A simple and sensitive method for the electrocatalytic detection of NADH on a carbon paste electrode modified with a redox-active (NC)(2)C(6)H(3)-NO/(NC)(2)C(6)H(3)-NHOH (NOPH/NHOHPH) electrogenerated in situ from 4-nitrophthalonitrile (4-NPHN) is presented. The electrode modified with 4-NPHN showed an efficient electrocatalytic activity towards the oxidation of NADH with activation overpotential of 0.12V vs. Ag/AgCl. The formation of an intermediate charge transfer complex is proposed for the charge transfer reaction between NADH and the 4-NPHN-resulting system. The second-order rate constant for electrocatalytic oxidation of NADH, kappa(obs), and the apparent Michaelis-Menten constant K(M), at pH 7.0 were evaluated with rotating disk electrode (RDE) experiments, giving 1.0x10(4)mol(-1)Ls(-1) and 2.7x10(-5)molL(-1), respectively. Employing the Koutecky-Levich approach indicated that the NADH oxidation reaction involves two electrons. The sensor provided a linear response range for NADH from 0.8 up to 8.5mumolL(-1) with sensitivity, detection, quantification limits and time response of 0.50muALmumol(-1), 0.25mumolL(-1), 0.82mumolL(-1) and 0.1s, respectively. The repeatability of the measurements with the same sensor and different sensors, evaluated in terms of relative standard deviation, were 4.1 and 5.0%, respectively, for n=10. 相似文献
The structures of ideal armchair (5,5) single-wall carbon nanotubes (SWCNTs) of different lengths (3.7, 8.8, and 16.0 Å for C40H20, C80H20, and C140H20) and with 1–10 hydroxyl groups at the end of the nanotube were fully optimized at the B3LYP/3-21G level, and in some cases at the B3LYP/6-31G* level, and the energy associated with the attachment of the OH substituent was determined. The OH-group attachment energy was compared with the OH functionalization of phenanthrene and picene models and with previous results for zigzag (9.0) SWCNT systems. In comparison to zigzag SWCNTs, the armchair form is more (by about 5 to 10 kcal mol?1) reactive toward hydroxylation.
Figure The structures of ideal armchair (5,5) single-wall carbon nanotubes (SWCNTs) of different lengths (3.7, 8.8, and 16.0 Å for C40H20, C80H20, and C140H20) and with 1–10 hydroxyl groups at the end of the nanotube were fully optimized at the B3LYP/3-21 G level, and in some cases at the B3LYP/6-31 G* level, and the energy associated with the attachment of the OH substituent was determined.
This study deals with the identification of glutamic acid by means of quantum chemical approach. FT-IR, FT-Raman and UV–vis spectra were recorded in the region 4000–400, 4000–50 cm? 1 and 200–600 nm, respectively. CAM-B3LYP/6-31G(d,p) and B2PLYP/6-31G(d,p) calculations were performed to obtain the optimised molecular structures, vibrational frequencies and corresponding vibrational assignment, thermodynamic properties and natural bonding orbital (NBO) analysis. The results show that the obtained optimised geometric parameters (bond lengths, bond angles and bond dihedrals) and vibrational frequencies were found to be in good agreement with the experimental results. The calculations of the electronic spectra were compared with the experimental ones. Furthermore, highest occupied molecular orbital and lowest unoccupied molecular orbital analyses and UV–vis spectral analysis were also performed to determine the energy band gaps and transition states. NBO analysis, calculated using density functional theory methods (CAM-B3LYP/6-31G(d,p) and B2PLYP/6-31G(d,p)), was induced to find inter-molecular atoms. 13C and 1H NMR isotropic chemical shifts were calculated and the assignments made were compared with the ChemDraw Ultra values. 相似文献