Simulation of the structure and dynamics of the bis(penicillamine) enkephalin zwitterion

Paul E. Smith, Liem X. Dang, Bernard Pettitt

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

We have performed a molecular dynamics simulation of the enkephalin derivative Tyr-(D)Pen-Gly-Phe-(D)Pen (DPDPE) in aqueous solvent. Electrostatic interactions were calculated with the Ewald method so as to accurately model the large interactions between the DPDPE zwitterion and the solvent and to avoid the use of electrostatic cutoff's or neutral chemical blocking groups. DPDPE is found to be extremely constrained with very little variation in the main-chain dihedral angles. Flexibility found in the region of the central glycine is greatly restricted compared with glycines in straight-chain peptides. Several conformational transitions are observed for the two aromatic side chains, indicating a high degree of flexibility in the side chains and that DPDPE does not have a single conformation in solution. This suggests that the arrangement of the tyrosine and phenylalanine aromatic residues in the bound conformation may be selected by the receptor environment. The main-chain conformation of DPDPE in solution has a parallel arrangement of peptide groups. This electrostatically unfavorable structure is stabilized by interactions of the carbonyls with the solvent. Solvent structure around the N terminus is found to be considerably localized, involving short ammonium cation to water contacts with lifetimes of the order of 50 ps or more. In comparison, water structure around the C terminus is much more mobile with lifetimes of the order of 20 ps or less.

Original languageEnglish (US)
Pages (from-to)67-73
Number of pages7
JournalJournal of the American Chemical Society
Volume113
Issue number1
StatePublished - Jan 2 1991
Externally publishedYes

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D-Penicillamine (2,5)-Enkephalin
Conformations
Peptides
Amino acids
Static Electricity
Glycine
glycylphenylalanine
Dihedral angle
Coulomb interactions
Water
Enkephalins
Molecular dynamics
Electrostatics
Molecular Dynamics Simulation
Phenylalanine
Ammonium Compounds
Positive ions
Tyrosine
Cations
Derivatives

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Simulation of the structure and dynamics of the bis(penicillamine) enkephalin zwitterion. / Smith, Paul E.; Dang, Liem X.; Pettitt, Bernard.

In: Journal of the American Chemical Society, Vol. 113, No. 1, 02.01.1991, p. 67-73.

Research output: Contribution to journalArticle

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