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Conformational equilibria in two poly-alanine and one lysine-doped poly-alanine peptide, [Ala8]⁺, [Ala16]⁺, and [Ac−(AAAAK)3A−NH2]³⁺, respectively, has been examined in both gas and water solution phase by computer simulation. The simulations studies were carried out using recently developed two-dimensional umbrella sampling techniques coupled to novel extended system multiple time step molecular dynamics methods. The efficiency of the latter method permitted run lengths greater than 30 ns to be used in the studies. The in vacuo simulation results are compared to recent novel gas-phase experimental studies employing drift tubes coupled to mass spectrometers (the injected-ion mobility/MS technique). Simulation studies of the peptides and neutralizing chloride anions solvated in computer water are compared to solution-phase NMR and ESR experimental work. Solvent effects are elucidated through a comparison of in vacuo and solution-phase simulation results. Comparisons between the results generated for the three different peptides are performed in order to assess the effect of the lysine side-chain and the position of the positive charge on peptide conformational equilibria in the two environments. The results indicate that the 3K peptide is roughly helical in a vacuum as well as in solution. The [Ala16]⁺ and [Ala8]⁺ form compact states in a vacuum in order to solvate the charge on the N-terminus. In water solution, the [Ala16]⁺ uncompacts but does not become strongly α-helical.

The results of computer simulation studies of CH3CO−(Ala)3−NHCH3 solvated in bulk computer water, solvated in computer water clusters, and in vacuo (isolated model molecule) at T = 300 K using modern computational methods are reported. The simulations were performed using a new multipurpose molecular dynamics package, PINY  MD, which utilizes recently developed simulation techniques and is capable of evolving the peptide−water system with an integration time step of 6 fs, 6 times the usual value. Specifically, the conformational free energy surface of the peptide is calculated via umbrella sampling using the distance between the carbonyl oxygen of the N-terminal blocking group and the amide hydrogen of the C-terminal blocking group as the reaction coordinate. Comparisons are made between results obtained using the several different force fields, CHARMM22 (MacKerell, A. D., Jr.; et al., unpublished), CHARMM19 (Brooks, B., et al. J. Comput. Chem 1983, 4, 187.) and AMBER95 (Cornell et al. J. Am. Chem. Soc. 1995, 117, 5179.). Contact is made with the early studies on this system under the conditions of constant temperature and volume using the CHARMM19 force field to model the interactions, a small system and spherical cutoff to treat the Coulombic interactions (Tobias, D. J.; Brooks, C. L., III Biochemistry 1991, 30, 6059−6070.). Quantitative results are presented on effects of finite size, the truncation of Coulombic interactions in periodic systems, and external pressure. Physically, the studies demonstrate quantitatively the effects of progressive hydration (moving the peptide from vacuum to clusters and into the bulk) on internal peptide hydrogen bonding.

Since Löffler in 1931 first drew attention to a condition characterized by transitory infiltration of the lung and eosinophilia, increasing interest has been paid to this symptom complex by those engaged in the treatment of diseases of the lung. Löffler's syndrome consists of four cardinal signs which have been present in all the cases so far reported: signs of pulmonary disease on auscultation and percussion, the presence of a corresponding shadow in the roentgenogram, transience of the pulmonary signs and increase of the eosinophils in the blood.One hundred and five cases have so far been reported, 51 by Löffler1 himself. The importance of this condition, from the point of view of both differential diagnosis and prognosis, induces us to report a case which came under our observation.The patient was a woman aged 25, of the asthenic type, 5 feet 81/2 inches (174 cm.) tall and weighing 126