Characterization of non-alpha helical conformations in Ala peptides

The folded (alpha helical) and unfolded (non-alpha helical) ensembles of the 21 amino acid peptide Ace-A21-Nme are characterized structurally. The replica exchange molecular dynamics approach is used to generate these ensembles at 46 different temperatures ranging from 278 to 487 K. Each replica system is simulated in explicit solvent for a period of 10 ns/replica, for a total of 460 ns. In addition to alpha helices, poly proline II (PPII) structures were identified to occur significantly. At low T the alpha helical content is larger than the PPII content, but near 300 K the PPII population is larger. Below 300 K, the PPII population increases with T, but it decreases above 300 K. The alpha helical content decreases with temperature. At temperatures below 300 K, there is a PPII propagation free energy that enhances the formation of long segments of PPII structure. This propagation term is smaller than for alpha helices. PPII segments of length 8 or less are more likely to form than alpha helices of the same length. The obtained low propensity for the formation of PPII segments of length shorter than five suggest that the interactions are responsible for the formation of PPII structures require a PPII segment of at least four amino acids. Stretches of four consecutive amino acids in the PPII conformations are needed for the formation of a groove around the peptide backbone that is strongly hydrated. Water in this groove is delocalized along a channel formed by the peptide in the PPII conformation.     

6H-SiC单晶中的蜷线

用PVT法制备了6H-SiC。用光学显微镜观察了晶体生长面的原生形貌。讨论了6H-SiC中蜷线的形状及其形成机理。蜷线起源于螺旋位错，它们的形状则决定于这些位错的符号与相对位置。在（0001）Si面上，蜷线表现为圆形螺旋，而在（0001）C面上则表现为六角形螺旋。通常情况下，蜷线的极点没有任何包裹物。然而在某些情况下，蜷线的极点会出现包裹物，如夹杂、微管、孔洞或者负晶等。当（0001）Si面作为生长面时，6H-SiC单晶的生长机制符合螺旋位错模型（BCF理论模型）。     

A simple method for predicting transmembrane {alpha} helices with better accuracy

The prediction of a protein's structure from its amino acidsequence has been a long-standing goal of molecular biology.In this work, a new set of conformational parameters for membranespanning helices was developed using the information from thetopology of 70 membrane proteins. Based on these conformationalparameters, a simple algorithm has been formulated to predictthe transmembrane helices in membrane proteins. A FORTRAN programhas been developed which takes the amino acid sequence as inputand gives the predicted transmembrane -helices as output. Thepresent method correctly identifies 295 transmembrane helicalsegments in 70 membrane proteins with only two overpredictions.Furthermore, this method predicts all 45 transmembrane helicesin the photosynthetic reaction center, bacteriorhodopsin andcytochrome c oxidase to an 86% level of accuracy and so is betterthan all other methods published to date.     

Peptide Architecture: Adding an α‐Helix to the PYY Lysine Side Chain Provides Nanomolar Binding and Body‐Weight‐Lowering Effects

The gut hormone PYY3‐36 influences food intake and body weight via interaction with hypothalamic presynaptic Y2 receptors (Y2R). Novel Y2R‐selective analogues of PYY3‐36 are therefore potential drug candidates for the treatment of obesity. It has been hypothesized that PYY3‐36 and possibly also the related PP‐fold peptides, NPY and PP, bind to the membrane via their amphipathic α‐helix prior to receptor interaction. The PYY3‐36 amphipathic α‐helix causes the peptide to associate with the membrane, making it essential for Y receptor potency as it potentially guides the C‐terminal pentapeptide into the correct conformation for receptor activation. Based on this hypothesis, the importance of the amphipathic nature of PYY3‐36, as well as the ability of amphipathic α‐helices to interact in solution to form di‐ and tetramers, we redesigned the peptide architecture by addition of an amphipathic α‐helix via the Lys 4 side chain of PYY3‐36. Two different amphipathic sequences were introduced; first, PYY17‐31, the native α‐helix of PYY, and secondly, its retro counterpart, PYY31‐17, which is also predicted to form an α‐helix. Moreover, several different turn motifs between the branching point and the additional α‐helix were tested. Several novel peptides with nanomolar Y2R binding affinities, as well as increased Y receptor selectivity, were identified. CD experiments showed the modifications to be well accepted, and an increase in mean ellipticity (ME) signifying an increased degree of α‐helicity was observed. Receptor binding experiments indicated that the direction of the additional α‐helix is less important, in contrast to the turn motifs, which greatly affect the Y1R binding and thus determine the Y1R activity. Conversely, the structure–activity relationships from in vivo data showed that the peptide containing the retro‐sequence was inactive, even though the binding data demonstrated high affinity and selectivity. This demonstrates that radical redesign of peptide architecture can provide nanomolar binding with improved subtype selectivity and with in vivo efficacy.