Quenched molecular dynamics simulations of tuftsin and proposed cyclic analogues

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

Research output: Contribution to journalArticle

71 Citations (Scopus)

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
StatePublished - 1992
Externally publishedYes

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Tuftsin
Lys-Pro-Arg-tuftsin
Molecular Dynamics Simulation
Molecular dynamics
Conformations
Computer simulation
Peptides
Temperature
Quenching
Derivatives

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Quenched molecular dynamics simulations of tuftsin and proposed cyclic analogues. / O'Connor, Stephen D.; Smith, Paul E.; Al-Obeidi, Fahad; Pettitt, Bernard.

In: Journal of Medicinal Chemistry, Vol. 35, No. 15, 1992, p. 2870-2881.

Research output: Contribution to journalArticle

O'Connor, Stephen D. ; Smith, Paul E. ; Al-Obeidi, Fahad ; Pettitt, Bernard. / Quenched molecular dynamics simulations of tuftsin and proposed cyclic analogues. In: Journal of Medicinal Chemistry. 1992 ; Vol. 35, No. 15. pp. 2870-2881.
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