Peptides orientational preferences

Very low-frequency vibrations have been observed in proteins (e.g., Brown et al., 1972 Genzel et al., 1976), which must involve concerted motion of rather large portions of the structure. By choosing a suitable set of proteins to measure (preferably in solution), it should be possible to decide approximately what structural modes are involved. Candidates include helix torsion, coupled changes of peptide orientation in /3 strands, and perhaps relative motions of entire domains or subunits. These hypotheses should be tested, because the low-frequency vibrations probably reflect large-scale structural properties that would be very useful to know. 

The interactions of several peptides with phospholipids have been studied by computer simulation. Emphasis has been given to several aspects of protein-phospholipid interactions, including the way of association and orientational preference of peptides in contact with a bilayer, the effect of phospholipids on the preference and stability of helical conformations, and the effect of the inserted peptide on the structure and dynamics of the phospholipids. These investigations have been extended to bundles of helices and even whole pore-forming proteins. In particular, the simulation of ion channels and of peptides with antimicrobial action has attracted a great deal of attention in theoretical studies. 

Because of the long time scales involved, it is currently not possible to simulate the process of peptide insertion at full atomic level description. As a consequence, in MD simulations a configuration is given, either parallel to the bilayer or inserted into it, and the evolution of the system is followed. Another approach is to perform simulations of orientational preference with the mean field approximation of lipids and water, retaining an atomic level description of the peptide. Several such simulations have been performed to determine the most likely mechanism of action for a given antimicrobial peptide. A recent review on simulations performed with antimicrobial peptides is given in ref. 78. 

Even though these enzymes have no absolute specificity, many of them show a preference for a particular side chain before the scissile bond as seen from the amino end of the polypeptide chain. The preference of chymotrypsin to cleave after large aromatic side chains and of trypsin to cleave after Lys or Arg side chains is exploited when these enzymes are used to produce peptides suitable for amino acid sequence determination and fingerprinting. In each case, the preferred side chain is oriented so as to fit into a pocket of the enzyme called the specificity pocket. 

The chelation effect also brings about a stabilization of the — 1 state of the peptide model complexes as indicated by the thermal stability and redox behavior. Only [Fe(Z-cys-Pro-Leu-cys-OMe)2] exhibits a relatively reversible redox couple in the cyclic voltammogram measurement, but the others do not (20). The bulkiness of side chains of the X and Y residues in Cys-X-Y-Cys probably restricts the adoption of the inherent by preferable conformation (ift = 0°), resulting in a more restricted orientation of Fe-S-C. In fact, the X-ray analysis of native rubredoxin shows that two of the Fe-S torsion angles are restricted and the other two are normal, i.e., conformationally more stable. 

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