Examination of the folding of a short alanine-based helical peptide with salt bridges using molecular dynamics simulation

Wei Zhou Wang, Topp Lin, Ying-Chieh Sun

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

A molecular dynamics simulation of the folding of a short alanine-based helical peptide of 17 residues with three Glu⋯Lys (i, i + 4) salt bridge pairs, referred to as the AEK17 peptide, was carried out. The simulation gave an estimated simulation folding time of 2.5 ns, shorter than 12 ns for an alanine-based peptide of 16 residues with three Lys residues only, referred to as the AK16 peptide, simulated previously. After folded, the AEK17 peptide had a helical content of 77%, in excellent agreement with the experimentally determined value of 80%. An examination of the folding pathways of AEK17 indicated that the peptide proceeded via three-turn helix conformations more than the helix-turn-helix conformation in the folding pathways. An analysis of interactions indicated that the formation of hydrogen bonds between Lys residue side chains and backbone carbonyls is a major factor in the abundant conformation of the three-turn helix intermediate. The substitution of three Ala with Glu residues reduces the extent of hydrophobic interaction in alanine-based AK peptides with the result that the breaking of the interactions of Lys ε-NH3+(side chain)⋯C=O(backbone) is a major activation action for the AEK17 to achieve a complete fold, in contrast to the AK16 peptide, in which breaking non-native hydrophobic interaction is the rate-determining step.

Original languageEnglish
Pages (from-to)3508-3514
Number of pages7
JournalJournal of Physical Chemistry B
Volume111
Issue number13
DOIs
Publication statusPublished - 2007 Apr 5

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alanine
Molecular Dynamics Simulation
Alanine
folding
Peptides
peptides
Molecular dynamics
Salts
examination
molecular dynamics
salts
Computer simulation
helices
simulation
Conformations
Hydrophobic and Hydrophilic Interactions
interactions
Hydrogen
Hydrogen bonds
Substitution reactions

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

Examination of the folding of a short alanine-based helical peptide with salt bridges using molecular dynamics simulation. / Wang, Wei Zhou; Lin, Topp; Sun, Ying-Chieh.

In: Journal of Physical Chemistry B, Vol. 111, No. 13, 05.04.2007, p. 3508-3514.

Research output: Contribution to journalArticle

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