Conformational Energy Calculations of the Effects of Sequence Variations on the Conformations of Two Tetrapeptides

István Simon, George Némethy, Harold A. Scheraga

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Conformational energy calculations were carried out on the two terminally blocked tetrapeptides N-acetyl-Thr-Asp-Gly-Lys-N'-methylamide and N-acetyl-Ala-Asp-Gly-Lys-N'-methylamide. The first peptide is a sequence variant of tetrapeptides studied earlier in this laboratory. The second peptide occurs in a bend at residues 94-97 in staphylococcal nuclease. A selection strategy is described which helps to accelerate the search of starting conformations used for energy minimization. The strategy involves exhaustive searches for conformations of fragments of the molecule which are stabilized by specific interactions and subsequent combination of fragments, prior to minimization. Several groups of low-energy conformations were found. They are compactly folded structures, but they differ from the “standard” chain reversals. One group, which is of low energy in both peptides, is stabilized by Asp···Asp and Asp···Lys backbone-side chain hydrogen bonds. Another group, of low energy in the Thr-containing peptides, is stabilized by a network of hydrogen bonds involving polar atoms of both backbone and side chains of the Thr, Asp, and Lys residues. The conformation corresponding to the sequence fragment in staphylococcal nuclease has relatively high energy, indicating that the bend observed in the protein is stabilized by interactions involving parts of the protein outside the tetrapeptide sequence.

Original languageEnglish
Pages (from-to)797-804
Number of pages8
Issue number4
Publication statusPublished - Jan 1 1978


ASJC Scopus subject areas

  • Organic Chemistry
  • Polymers and Plastics
  • Inorganic Chemistry
  • Materials Chemistry

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