Quenched Molecular Dynamics Simulations of Tuftsin and Proposed Cyclic Analogs

Stephen D. O'Connor, Paul E. Smith, Fahad Al-Obeidi, B. Montgomery Pettitt

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Abstract

We have used high-temperature quenched molecular dynamics calculations to investigate the conformational properties of tuftsin (Thr-Lys-Pro-Arg) in solution. Conformers obtained after quenching of the dynamical structures were sorted into families depending on their relative energies and backbone conformations. By examination of these families, several cyclic analogues of tuftsin were proposed and examined theoretically by further quenched dynamics simulations. Two of the four proposed analogues were found to adopt essentially identical conformations to that of linear tuftsin. It is suggested that these two derivatives (cyclo[Thr-Lys-Pro-Arg-Gly] and cyclo[Thr-Lys-Pro-Arg-Asp]) may be biologically active, and that the introduction of cyclic conformational constraints should help to reduce the entropic penalty to peptide binding.

Original languageEnglish (US)
Pages (from-to)2870-2881
Number of pages12
JournalJournal of Medicinal Chemistry
Volume35
Issue number15
DOIs
StatePublished - Jul 1 1992

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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