Theoretical calculation of polarizability isotope effects

We propose a scheme to estimate hydrogen isotope effects on molecular polarizabilities. This approach combines the any-particle molecular orbital method, in which both electrons and H/D nuclei are described as quantum waves, with the auxiliary density perturbation theory, to calculate analytically the polarizability tensor. We assess the performance of method by calculating the polarizability isotope effect for 20 molecules. A good correlation between theoretical and experimental data is found. Further analysis of the results reveals that the change in the polarizability of a X-H bond upon deuteration decreases as the electronegativity of X increases. Our investigation also reveals that the molecular polarizability isotope effect presents an additive character. Therefore, it can be computed by counting the number of deuterated bonds in the molecule.     

Effect of pressure on deuterium isotope effects of yeast alcohol dehydrogenase: evidence for mechanical models of catalysis

Moderate pressure accelerates hydride transfer catalyzed by yeast alcohol dehydrogenase, indicative of a large negative volume of activation [Cho and Northrop (1999) Biochemistry 38, 7470-7475]. A comparison of the effects of pressure on the oxidation of normal versus dideuteriobenzyl alcohol generates a monophasic decrease in the intrinsic isotope effect; therefore, the volume of activation for the transition-state of deuteride transfer must be even more negative, by 10.4 mL/mol. This finding appears consistent with hydrogen tunneling previously proposed for this dehydrogenase [Cha, Y., Murray, C. J., and Klinman, J. P. (1989) Science 243, 1325-1330]. However, a global fit of the primary data shows that the entire isotope effect arises from a transition-state phenomenon, unlike normal isotope effects, which arise from different vibrational frequencies in reactant states, and tunneling isotope effects, which arise from a mixture of both states. Assuming the phenomenon is tunneling, the isotopic data are consistent with a Bell tunneling correction factor of Q(H) = 12 and an imaginary frequency of nu(H) = 1220 cm(-1), the first so calculated from experimental enzymatic data. This excessively large correction factor and the large difference in the isotopic activation volumes, plus the low isotope effects at extrapolated pressures, challenge traditional applications of physical organic chemistry and transition-state theory to enzymatic catalysis. They suggest instead that something other than transition-state stabilization or tunneling is responsible for the rate acceleration, something unique to the enzymatic transition state that does not occur in nonenzymatic reactions. Arguments for the vibrational model of coupled atomic motions and the fluctuating enzyme model of protein domain motion are put forward as possible interpretations.     

Biotypes of Hessian fly (Dipt., Cecidomyiidae) in Morocco

Hessian fly, Mayetiola destructor (Say), is the most important insect pest of wheat in Morocco, where host plant resistance has been used successfully for control. Our objective was to determine the frequency of Hessian fly virulence on H5, H13 and H22 resistance genes. Five Hessian fly populations from the principal cereal‐growing regions in Morocco were studied. The variability in percentage of susceptible plants across Hessian fly populations was highly significant (P < 0.01), indicating differences in virulence frequencies. Plants with the H13 gene had the lowest percentage of susceptible plants, 1.77 and 1.51%, when infested with Hessian flies from Fes and Marchouch, respectively. A low level of virulence to H22 was detected in Fes, Abda and Marchouch populations, 1.87, 1.54 and 1.99% susceptible plants, respectively. The level of virulence to H5 was low in all the five populations. The Beni Mellal population gave the highest percentage of susceptible plants carrying H13 and H22 genes, 6.43 and 7.28%, respectively. The size of live larvae on susceptible plants of the three cultivars carrying H5, H13 and H22 was similar to that of the susceptible check, indicating that a true virulence (biotype) is developing in Hessian fly populations in Morocco. Thus, continuous monitoring of the development of Hessian fly biotypes is essential for optimal deployment of resistance genes.     

Theoretical study of the decomposition mechanisms and kinetics of the ingredients RDX in composition B

RDX as a component in composition B (TNT + RDX) was first studied by us on its mechanism and kinetics of decomposition reactions in this paper. We have pointed out three possible pathways and found a new low-energy process of its decomposition. The N-N bond cleavage in composition B has higher dissociation energies than the monomer, but it is also the initial step. The optimized structures and the frequencies of all the stationary points were calculated at the B3LYP/6-31G(d) level. The minimum-energy paths were obtained by using the intrinsic reaction coordinate (IRC) theory, and the reaction potential energy curve was corrected with zero-point energy. Finally, the rate constants were calculated in a wide temperature region from 200 to 2500 K using TST, TST/Eckart theories. The obtained results also indicate that the tunneling effects are remarkable at low temperature (200 K 相似文献   

Harmonic force field for nitro compounds

Molecular simulations leading to sensors for the detection of explosive compounds require force field parameters that can reproduce the mechanical and vibrational properties of energetic materials. We developed precise harmonic force fields for alanine polypeptides and glycine oligopeptides using the FUERZA procedure that uses the Hessian tensor (obtained from ab initio calculations) to calculate precise parameters. In this work, we used the same procedure to calculate generalized force field parameters of several nitro compounds. We found a linear relationship between force constant and bond distance. The average angle in the nitro compounds was 116°, excluding the 90° angle of the carbon atoms in the octanitrocubane. The calculated parameters permitted the accurate molecular modeling of nitro compounds containing many functional groups. Results were acceptable when compared with others obtained using methods that are specific for one type of molecule, and much better than others obtained using methods that are too general (these ignore the chemical effects of surrounding atoms on the bonding and therefore the bond strength, which affects the mechanical and vibrational properties of the whole molecule).     

A reproductive fitness cost associated with Hessian fly (Diptera: Cecidomyiidae) virulence to wheat's H gene-mediated resistance

We studied whether adaptation of the Hessian fly, Mayetiola destructor (Say) (Diptera: Cecidomyiidae), to plant resistance incurs fitness costs. In this gene-for-gene interaction, adaptation to a single H resistance gene occurs via loss of a single effector encoded by an Avirulence gene. By losing the effector, the adapted larva now survives on the H gene plant, presumably because it evades the plant's H gene-mediated surveillance system. The problem is the Hessian fly larva needs its effectors for colonization. Thus, for adapted individuals, there may be a cost for losing the effector, with this then creating a trade-off between surviving on H-resistant plants and growing on plants that lack H genes. In two different tests, we used wheat lacking H genes to compare the survival and growth of a nonadapted strain to two H-adapted strains. The two adapted strains differed in that one had been selected for adaptation to H9, whereas the other strain had been selected for adaptation to H13. Tests showed that two H-adapted strains were similar to the nonadapted strain in egg-to-adult survival but that they differed in producing adults with smaller wings. By using known relationships between wing length and reproductive potential, we found that losses in wing length underestimate losses in reproductive potential. For example, H9- and H13-adapted females had 9 and 3% wing losses, respectively, but they were estimated to have 32 and 12% losses in egg production. Fitness costs of adaptation will be investigated further via selection experiments comparing Avirulence allele frequencies for Hessian fly populations exposed or not exposed to H genes.     

Relationship between the shape and density distribution of the femur and its natural frequencies of vibration

It has been recently suggested that mechanical loads applied at frequencies close to the natural frequencies of bone could enhance bone apposition due to the resonance phenomenon. Other applications of bone modal analysis are also suggested. For the above-mentioned applications, it is important to understand how patient-specific bone shape and density distribution influence the natural frequencies of bones. We used finite element models to study the effects of bone shape and density distribution on the natural frequencies of the femur in free boundary conditions. A statistical shape and appearance model that describes shape and density distribution independently was created, based on a training set of 27 femora. The natural frequencies were then calculated for different shape modes varied around the mean shape while keeping the mean density distribution, for different appearance modes around the mean density distribution while keeping the mean bone shape, and for the 27 training femora. Single shape or appearance modes could cause up to 15% variations in the natural frequencies with certain modes having the greatest impact. For the actual femora, shape and density distribution changed the natural frequencies by up to 38%. First appearance mode that describes the general cortical bone thickness and trabecular bone density had one of the strongest impacts. The first appearance mode could therefore provide a sensitive measure of general bone health and disease progression. Since shape and density could cause large variations in the calculated natural frequencies, patient-specific FE models are needed for accurate estimation of bone natural frequencies.     

Zwitterionic conformers of pyrrolysine and their interactions with metal ions—a theoretical study

A total of 16 pyrrolysine conformers in their zwitterionic forms are studied in gas and simulated aqueous phase using a polarizable continuum model (PCM). These conformers are selected on the basis of our study on the intrinsic conformational properties of non-ionic pyrrolysine molecule in gas phase [Das and Mandal (2013) J Mol Model 19:1695?1704]. In aqueous phase, the stable zwitterionic pyrrolysine conformers are characterized by full geometry optimization and vibrational frequency calculations using B3LYP/6-311++G(d,p) level of theory. Single point calculations are also carried out at MP2/6-311++G(d,p) level. Characteristic intramolecular hydrogen bonds present in each conformer, their relative energies, theoretically predicted vibrational spectra, rotational constants and dipole moments are systematically reported. The calculated relative energy range of the conformers at B3LYP/6-311++G(d,p) level is 5.19 kcal mol^?1 whereas the same obtained by single point calculations at MP2/6-311++G(d,p) level is 4.58 kcal mol^?1. A thorough analysis reveals that four types of intramolecular H-bonds are present in the conformers; all of which play key roles in determining the energetics and in imparting the observed conformations to the conformers. The vibrational frequencies are found to shift invariably toward the lower side of frequency scale corresponding to the presence of the H-bonds. This study also points out that conformers with diverse structural motifs may differ in their thermodynamical stability by a narrow range of relative energy. The effects of metal coordination on the relative stability order and structural features of the conformers are examined by complexing five zwitterionic conformers of pyrrolysine with Cu⁺² through their carboxylate groups. The interaction enthalpies and Gibbs energies, rotational constants, vibrational frequencies and dipole moments of the metal complexes calculated at B3LYP level are also reported. The zwitterionic conformers of pyrrolysine are not stable in gas phase; after geometry optimization they are converted to the non-ionic forms.     

An improved generalized AMBER force field (GAFF) for urea

We describe an improved force field parameter set for the generalized AMBER force field (GAFF) for urea. Quantum chemical computations were used to obtain geometrical and energetic parameters of urea dimers and larger oligomers using AM1 semiempirical MO theory, density functional theory at the B3LYP/6-31G(d,p) level, MP2 and CCSD ab initio calculations with the 6-311++G(d,p), aug-cc-pVDZ, aug-cc-pVTZ, and aug-cc-pVQZ basis sets, and with the CBS-QB3 and CBS-APNO complete basis set methods. Seven different urea dimer structures were optimized at the MP2/aug-cc-pVDZ level to obtain accurate interaction energies. Atomic partial charges were calculated at the MP2/aug-cc-pVDZ level with the restrained electrostatic potential (RESP) fitting approach. The interaction energies computed with these new RESP charges in the force field are consistent with those obtained from CCSD and MP2 calculations. The linear dimer structure calculated using the force field with modified geometrical parameters and the new RESP charge set agrees well with available experimental data.     

Equilibrium perturbation by isotope substitution.

When malic enzyme is added to a mixture of malate-2-d, TPN, CO2, pyruvate, and TPNH at concentrations calculated to be at equilibrium, the TPNH level first drops and then increases slowly to its original level. This equilibrium perturbation is caused by slower cleavage of C-D than C-H bonds during hydride transfer as malate-2-d and TPNH are partly converted into TPND and malate-2-h in the process of establishing isotopic equilibrium. With malate-2-d, isotope effects for malic enzyme at pH 7.1 and malate dehydrogenase at pH 9.3 of 1.45 and 1.70-2.16 (depending on oxaloacetate level) were determined with this method, while the corresponding isotope effects on V/Kmalate and V for the chemical reactions were 1.5-1.8 and 1.0, and 1.9 and 1.5 for the two enzymes. The advantage of this method is its extreme sensitivity, and the lack of interference from various artifacts. The sensitivity is sufficient to permit determination of 13C and 15N isotope effects in favorable cases, and values of 1.031 for malic enzyme with 13CO2, and 1.047 for glutamate dehydrogenase with 15NH4+ have been determined. In the course of this work it was discovered that the equilibrium constants for oxidation by DPN, and oxidative decarboxylation by TPN are lower for malate-2-d than for malate-2-h by a factor of 0.76-0.82. Changes in Keq upon deuterium substitution, which are predicted by the calculations of Hartshorn and Shiner (1972), should be observed for many other reactions as well.     

Genotype frequencies associated with incompatibility systems in tristylous plants

A general procedure has been given previously for calculating frequencies of the morphs Long, Mid, and Short in equilibrium populations of tristylous plants. It is now demonstrated that an equilibrium state actually exists at the genotype level if this procedure produces admissible morph frequencies. This result holds in a diploid model, with or without linkage between the two loci involved. It is shown how the genotype frequencies may be determined for any set of mating probabilities. It is also explained how these frequencies may be calculated in a tetraploid model incorporating double reduction. The general theory is applied to a particular situation where the Mid morph is at a selective disadvantage as a seed parent.     

Analysis of the separation of gadolinium isotopes by the ICR method

The problem of separating gadolinium isotopes is discussed. The parameters of isotope separation in a plasma by the ICR method are estimated for a device with given operating parameters. The mean transverse energy 〈E_⊥〉 of the heated ions of the ¹⁵⁷Gd isotope and the heating efficiency η are calculated as functions of the frequency of the RF electric field in the plasma. The dependence of the heating efficiency η on the longitudinal temperature of the plasma flow is investigated. The issue of how the concentration of the target isotope ions at the collector plate depends on the longitudinal coordinate measured from the front edge of the plate is analyzed for different values of the frequency detuning parameter. The extraction coefficient Г for the target isotope is calculated as a function of the distance b between the collector plates for different frequency detunings.     

Estimating the carbonyl anharmonic vibrational frequency from affordable harmonic frequency calculations

A linear correlation between harmonic and anharmonic frequencies of water calculated at B3LYP level of theory was observed with a number of basis sets. Similar relationships were found in both the gas phase and solution for several small molecules. The best correlation was found for C = O stretch mode in formaldehyde, formamide and N-methylacetamide. The average difference between B3LYP harmonic and anharmonic ν(C = O) frequencies calculated with several basis sets in these molecules was 30 cm(-1). The ad hoc correction of -30 cm(-1), added to harmonic frequencies of two different carbonyl groups present in a structure of a larger molecule was tested as a fast way of predicting anharmonic frequencies without elaborated calculations. The proposed approach was tested successfully on a larger molecule of E and Z isomers of N-acetyl-α,β-dehydrophenylalanine N',N'-dimethylamide [Ac-(E/Z)-ΔPhe-NMe(2)] and the estimated anharmonic ν(C = O) frequencies were close to directly calculated results.     

Insights into the mechanism of flavoprotein-catalyzed amine oxidation from nitrogen isotope effects on the reaction of N-methyltryptophan oxidase

The mechanism of N-methyltryptophan oxidase, a flavin-dependent amine oxidase from Escherichia coli, was studied using a combination of kinetic isotope effects and theoretical calculations. The 15(kcat/Km) kinetic isotope effect for sarcosine oxidation is pH-dependent with a limiting value of 0.994-0.995 at high pH. Density functional theory calculations on model systems were used to interpret these isotope effects. The isotope effects are inconsistent with proposed mechanisms involving covalent amine-flavin adducts but cannot by themselves conclusively distinguish between some discrete electron-transfer mechanisms and a direct hydride-transfer mechanism, although the latter mechanism is more consistent with the energetics of the reaction.     

Human erythrocyte glutathione reductase: chemical mechanism and structure of the transition state for hydride transfer

Kinetic parameters and primary deuterium kinetic isotope effects for NADH and five pyridine nucleotide substrates have been determined at pH 8.1 for human erythrocyte glutathione reductase. DV/KNADH and DV are equal to 1.4 and are pH independent below pH 8.1, but DV decreases to 1.0 at high pH as a group exhibiting a pK of 8.6 is deprotonated. This result suggests that as His-467' is deprotonated, the rate of the isotopically insensitive oxidative half-reaction is specifically decreased and becomes rate-limiting. For all substrates, equivalent V and V/K primary deuterium kinetic isotope effects are observed at pH values below 8.1. The primary deuterium kinetic isotope effect on V, but not V/K, is sensitive to solvent isotopic composition. The primary tritium kinetic isotope effects agree well with the corresponding value calculated from the primary deuterium kinetic isotope effects by using the Swain-Schaad relationship. This suggests that the primary deuterium kinetic isotope effects observed in these steady-state experiments are the intrinsic primary deuterium kinetic isotope effects for hydride transfer. The magnitude of the primary deuterium kinetic isotope effect is dependent on the redox potential of the pyridine nucleotide substrate used, varying from approximately 1.4 for NADH and -320 mV reductants to 2.7 for thioNADH to 4.2-4.8 for 3-acetylpyridine adenine dinucleotide (3APADH). The alpha-secondary tritium kinetic isotope effects also increase as the redox potential of the pyridine nucleotide substrate becomes more positive. Together, these data indicate that the transition state for hydride transfer is very early for NADH and becomes later for thioNADH and 3APADH, as predicted by Hammond's postulate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combining evolutionary and structural information for local protein structure prediction

We study the effects of various factors in representing and combining evolutionary and structural information for local protein structural prediction based on fragment selection. We prepare databases of fragments from a set of non-redundant protein domains. For each fragment, evolutionary information is derived from homologous sequences and represented as estimated effective counts and frequencies of amino acids (evolutionary frequencies) at each position. Position-specific amino acid preferences called structural frequencies are derived from statistical analysis of discrete local structural environments in database structures. Our method for local structure prediction is based on ranking and selecting database fragments that are most similar to a target fragment. Using secondary structure type as a local structural property, we test our method in a number of settings. The major findings are: (1) the COMPASS-type scoring function for fragment similarity comparison gives better prediction accuracy than three other tested scoring functions for profile-profile comparison. We show that the COMPASS-type scoring function can be derived both in the probabilistic framework and in the framework of statistical potentials. (2) Using the evolutionary frequencies of database fragments gives better prediction accuracy than using structural frequencies. (3) Finer definition of local environments, such as including more side-chain solvent accessibility classes and considering the backbone conformations of neighboring residues, gives increasingly better prediction accuracy using structural frequencies. (4) Combining evolutionary and structural frequencies of database fragments, either in a linear fashion or using a pseudocount mixture formula, results in improvement of prediction accuracy. Combination at the log-odds score level is not as effective as combination at the frequency level. This suggests that there might be better ways of combining sequence and structural information than the commonly used linear combination of log-odds scores. Our method of fragment selection and frequency combination gives reasonable results of secondary structure prediction tested on 56 CASP5 targets (average SOV score 0.77), suggesting that it is a valid method for local protein structure prediction. Mixture of predicted structural frequencies and evolutionary frequencies improve the quality of local profile-to-profile alignment by COMPASS.     

Transition energy and potential energy curves for ionized inner-shell states of CO, O2 and N2 calculated by several inner-shell multiconfigurational approaches

Potential energy curves and inner-shell ionization energies of carbon monoxide, oxygen and nitrogen molecules were calculated using several forms of the inner-shell multiconfigurational self-consistent field (IS-MCSCF) method—a recently proposed protocol to obtain specifically converged inner-shell states at this level. The particular forms of the IS-MCSCF method designated IS-GVB-PP, IS-FVBL and IS-CASSCF stand for perfect pairing generalized valence bond, full valence bond-like MCSCF and complete active space self consistent field, respectively. A comparison of these different versions of the IS-MCSCF method was carried out for the first time. The results indicate that inner-shell states are described accurately even for the simplest version of the method (IS-GVB-PP). Dynamic correlation was recovered by multireference configuration interaction or multireference perturbation theory. For molecules not having equivalent atoms, all methods led to comparable and accurate transition energies. For molecules with equivalent atoms, the most accurate results were obtained by multireference perturbation theory. Scalar relativistic effects were accounted for using the Douglas-Kroll-Hess Hamiltonian.