Evaluating the active site-substrate interplay between x-ray crystal structure and molecular dynamics in chorismate mutase.

Designing realistic quantum mechanical (QM) models of enzymes is dependent on reliably discerning and modeling residues, solvents, and cofactors important in crafting the active site microenvironment. Interatomic van der Waals contacts have previously demonstrated usefulness toward designing QM-models, but their measured values (and subsequent residue importance rankings) are expected to be influenceable by subtle changes in protein structure. Using chorismate mutase as a case study, this work examines the differences in ligand-residue interatomic contacts between an x-ray crystal structure and structures from a molecular dynamics simulation. Select structures are further analyzed using symmetry adapted perturbation theory to compute ab initio ligand-residue interaction energies. The findings of this study show that ligand-residue interatomic contacts measured for an x-ray crystal structure are not predictive of active site contacts from a sampling of molecular dynamics frames. In addition, the variability in interatomic contacts among structures is not correlated with variability in interaction energies. However, the results spotlight using interaction energies to characterize and rank residue importance in future computational enzymology workflows.

Ab Initio Study of Chiral Discrimination in the Glycidol Dimer.

Chiral discrimination, the ability of a chiral molecule to exhibit different weak intermolecular interactions than its mirror image, is investigated for dimers of oxiranemethanol (glycidol). In this regard, high-level ab initio calculations were performed to study the chiral recognition effects in the homochiral and heterochiral dimers of glycidol. Fourteen dimer structures, seven homochiral and seven heterochiral, were studied: they all feature two intermolecular O-H···O hydrogen bonds. These structures have been determined with the second-order Møller-Plesset perturbation theory (MP2) using the aug-cc-pVTZ basis set and verified to pertain to actual local minima. The benchmark interaction energy values were computed using MP2 extrapolated from the aug-cc-pVQZ and aug-cc-pV5Z bases with a higher-level correction from a coupled-cluster calculation in the aug-cc-pVTZ basis. The global minimum structure is a homochiral one, with the two hydrogen bonds forming a part of a ring with eight heavy atoms. A similar heterochiral structure has a binding energy smaller by about 0.6 kcal/mol. The largest diastereomeric energy difference is about 1.0 kcal/mol. Further insight into the origins of chiral discrimination was provided by symmetry-adapted perturbation theory (SAPT) and a functional-group SAPT (F-SAPT) difference analysis to investigate the direct and indirect effects of two -H/-CH2OH substitutions leading from an achiral ethylene oxide dimer to the chiral glycidol dimer. Last but not least, harmonic frequency shifts relative to a noninteracting glycidol molecule were calculated and analyzed for all conformations to get insight into the origins of chiral discrimination. It is found that the largest frequency shifts are related to the effect of hydrogen bonding on the O-H stretch mode, the stability of the ring involving both hydrogen bonds, and the transition between two nonequivalent minima of the glycidol molecule.

Chiral Self Recognition: Interactions in Propylene Oxide Complexes.

We elucidate the subtle energetic effects that give rise to chiral recognition in the propylene oxide dimer. Specifically, we investigate six homochiral (RRx) and six heterochiral (RSx) structures of this complex, with the RRn-RSn pair sharing the same pattern of weak O···H-C hydrogen bonds but subtly differing in energy due to chiral effects. The interaction energies for the 12 structures are computed at various levels of electronic structure theory and basis set up to the complete basis set limit of the coupled-cluster approach with single, double, and perturbative triple excitations (CCSD(T)). These benchmark interaction energies are compared to the results of various approximate approaches, both density functional theory-based and wave function-based. We find that while the RRn-RSn diastereomeric energy differences exhibit a great deal of error cancellation between the individual interaction energies, most approximate methods have a hard time even reproducing the correct signs of these differences consistently. The origins of the RRn-RSn differences are elucidated by several symmetry-adapted perturbation theory (SAPT) analyses ranging from ordinary intermolecular SAPT to a functional-group SAPT (F-SAPT) decomposition of direct and indirect H → CH3 substitution effects leading from achiral ethylene oxide complexes to chiral propylene oxide ones. It is shown that the largest diastereomeric energy differences are correlated to the variations in the electrostatic and dispersion SAPT contributions. Finally, the effect of chiral interactions on the vibrational frequencies of a propylene oxide molecule is investigated, showing that the interaction results in largest frequency shifts, splittings, and chiral discrimination effects in the lowest, torsional vibrational mode of the noninteracting monomer.

The Effect of Smoking on Mast Cells Density and Angiogenesis in Chronic Periodontitis.

BACKGROUND AND OBJECTIVE: Gingival bleeding reduction in smokers has been associated with decreased blood vessel density. The mechanism of suppressive effect of cigarette smoking on blood vessel density is not precisely defined. The aim of this study was to evaluate the impact of smoking on angiogenesis by assessing mast cells density and VEGF expression in chronic periodontitis. MATERIALS& METHODS: 52 paraffin embedded block of gingiva tissues with periodontitis obtained from 30 nonsmokers and 22 smokers undergoing flap surgery were examined immunohistochemically for VEGF expression. Mast cell counts was completed on toluidine blue stained slides. Exposure to cigarette smoking was calculated by the number of packs × year. Patients were classified into 4 groups based on the number of smoked cigarettes. The correlation between VEGF expression and mast cell counts was evaluated and compared in nonsmokers and smokers. RESULTS: The mean number of mast cells (p=0.004) and average value of VEGF expression (p = 0.000) in nonsmokers was significantly higher than smokers. No correlation was noted between VEGF expression / mast cell counts and number of smoked cigarettes in four groups of smokers (p=0.29,0.12 , 0.20 and 0.11, respectively). CONCLUSION: Mast cells and VEGF expression may account for suppressive effect of cigarette smoking on blood vessels in periodontitis.

Short-term bulk energy storage system scheduling for load leveling in unit commitment: modeling, optimization, and sensitivity analysis.

Energy storage systems (ESSs) have experienced a very rapid growth in recent years and are expected to be a promising tool in order to improving power system reliability and being economically efficient. The ESSs possess many potential benefits in various areas in the electric power systems. One of the main benefits of an ESS, especially a bulk unit, relies on smoothing the load pattern by decreasing on-peak and increasing off-peak loads, known as load leveling. These devices require new methods and tools in order to model and optimize their effects in the power system studies. In this respect, this paper will model bulk ESSs based on the several technical characteristics, introduce the proposed model in the thermal unit commitment (UC) problem, and analyze it with respect to the various sensitive parameters. The technical limitations of the thermal units and transmission network constraints are also considered in the model. The proposed model is a Mixed Integer Linear Programming (MILP) which can be easily solved by strong commercial solvers (for instance CPLEX) and it is appropriate to be used in the practical large scale networks. The results of implementing the proposed model on a test system reveal that proper load leveling through optimum storage scheduling leads to considerable operation cost reduction with respect to the storage system characteristics.