Structure of Penta-Alanine Investigated by Two-Dimensional Infrared Spectroscopy and Molecular Dynamics Simulation.

We have studied the structure of (Ala)5, a model unfolded peptide, using a combination of 2D IR spectroscopy and molecular dynamics (MD) simulation. Two different isotopomers, each bis-labeled with (13)C═O and (13)C═(18)O, were strategically designed to shift individual site frequencies and uncouple neighboring amide-I' modes. 2D IR spectra taken under the double-crossed ⟨π/4, -π/4, Y, Z⟩ polarization show that the labeled four-oscillator systems can be approximated by three two-oscillator systems. By utilizing the different polarization dependence of diagonal and cross peaks, we extracted the coupling constants and angles between three pairs of amide-I' transition dipoles through spectral fitting. These parameters were related to the peptide backbone dihedral angles through DFT calculated maps. The derived dihedral angles are all located in the polyproline-II (ppII) region of the Ramachandran plot. These results were compared to the conformations sampled by Hamiltonian replica-exchange MD simulations with three different CHARMM force fields. The C36 force field predicted that ppII is the dominant conformation, consistent with the experimental findings, whereas C22/CMAP predicted similar population for α+, ß, and ppII, and the polarizable Drude-2013 predicted dominating ß structure. Spectral simulation based on MD representative conformations and structure ensembles demonstrated the need to include multiple 2D spectral features, especially the cross-peak intensity ratio and shape, in structure determination. Using 2D reference spectra defined by the C36 structure ensemble, the best spectral simulation is achieved with nearly 100% ppII population, although the agreement with the experimental cross-peak intensity ratio is still insufficient. The dependence of population determination on the choice of reference structures/spectra and the current limitations on theoretical modeling relating peptide structures to spectral parameters are discussed. Compared with the previous results on alanine based oligopeptides, the dihedral angles of our fitted structure, and the most populated ppII structure from the C36 simulation are in good agreement with those suggesting a major ppII population. Our results provide further support for the importance of ppII conformation in the ensemble of unfolded peptides.

The Relationship between Smoking Status and Suicidal Behavior in Korean Adults: The 4th Korea National Health and Nutrition Examination Survey (2007-2009).

BACKGROUND: This study was performed to evaluate the relationship between smoking status and suicidal ideations or suicide attempts in Korean adults. METHODS: The study used data from the 4th Korea National Health and Nutrition Examination Survey, and involved 17,065 participants. We used multiple logistic regression analysis to evaluate the relationship between smoking status and suicidal behavior. The results were adjusted for covariates including depression and physical disease. RESULTS: After adjusting for covariates, current smokers (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.34 to 2.05) and former smokers (OR, 1.39; 95% CI, 1.13 to 1.72) proved more likely to have suicidal ideations than non-smokers. Among women, current smokers (OR, 2.00; 95% CI, 1.47 to 2.72) and former smokers (OR, 1.48; 95% CI, 1.11 to 1.99) were more likely to have suicidal ideations than non-smokers. However, among the men there was no significant relationship between smoking status and suicidal ideations. Among all the participants who had had suicidal ideations, there was a significant relationship between current smoking and suicide attempts (OR, 1.80; 95% CI, 1.05 to 3.07). There was also a relationship between current smoking and suicide attempts among women (OR, 2.40; 95% CI, 1.31 to 4.37), but no significant relationship among men. CONCLUSION: There is a relationship between smoking status and suicidal ideations and suicide attempts in the general population of Korea. This relationship is particularly clear in women, and is independent of comorbid chronic disease and depression. Current smokers and former smokers are more likely to have suicidal ideations than non-smokers; current smokers are also more likely to have attempted suicide.

Re-evaluation of the reported experimental values of the heat of vaporization of N-methylacetamide.

The accuracy of empirical force fields is inherently related to the quality of the target data used for optimization of the model. With the heat of vaporization (ΔH(vap)) of N-methylacetamide (NMA), a range of values have been reported as target data for optimization of the nonbond parameters associated with the peptide bond in proteins. In the present work, the original experimental data and Antoine constants used for the determination of the ΔH(vap) of NMA are reanalyzed. Based on this analysis, the wide range of ΔH(vap) values reported in the literature are shown to be due to incorrect reporting of the temperatures at which the original values were extracted and limitations in the quality of experimental vapor pressure-temperature data over a wide range of temperatures. Taking these problems into account, a consistent ΔH(vap) value is extracted from three studies for which experimental data are available. This analysis suggests that the most reliable value for ΔH(vap) is 13.0±0.1 at 410 K for use in force field optimization studies. The present results also indicate that similar analyses, including analysis of Antoine constants alone, may be of utility when reported ΔH(vap) values are not consistent for a given neat liquid.