Characterization of the stereochemical selectivity of β-hairpin formation by molecular dynamics simulations

Patricia Soto, Ronen Zangi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The stability of secondary structure motifs found in proteins is influenced by the choice of the configuration of the chiral centers present in the amino acid residues (i.e., D vs L). Experimental studies showed that the structural properties of the tetrapeptide LV LP LA LL (all-L) are drastically altered upon mutating the L-proline and the L-alanine by their D-enantiomers [J. Am. Chem. Soc. 1996, 118, 6975]. The all-L diastereomer is unstructured, experiencing little or no β-hairpin formation, while the LV DP DA LL peptide exhibits a substantial population of β-hairpin conformation. In this study, we perform molecular dynamics simulations to investigate the folding propensity of these two model peptides. The results confirm the experimental findings, namely, that the presence of D-amino acids in the loop region strongly induces β-hairpin formation (a population increase from about 1.5% to 50% is observed). The major factor determining the different behavior is found to be the large difference in energy between the two diastereomers, approximately 22 kJ/mol, when they adopt a β-hairpin structure. The higher energy observed for the all-L peptide is a consequece of none-ideal hydrogen bond formation and of steric repulsions. The results suggest that selective incorporation of D-amino acids in proteins can be used to enhance certain secondary structure elements. The kinetic behavior of the folding process observed in the simulations is also investigated. We find that the decay rate of the folded structure fits to a biexponential function, suggesting that the folding/unfolding process of a β-hairpin is governed by two different mechansims.

Original languageEnglish
Pages (from-to)1281-1288
Number of pages8
JournalJournal of Physical Chemistry B
Volume109
Issue number3
DOIs
StatePublished - Jan 27 2005

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folding
Peptides
peptides
amino acids
Molecular dynamics
Amino acids
selectivity
molecular dynamics
Amino Acids
Computer simulation
proteins
Proteins
Enantiomers
simulation
enantiomers
alanine
Proline
Alanine
decay rates
Conformations

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry

Cite this

Characterization of the stereochemical selectivity of β-hairpin formation by molecular dynamics simulations. / Soto, Patricia; Zangi, Ronen.

In: Journal of Physical Chemistry B, Vol. 109, No. 3, 27.01.2005, p. 1281-1288.

Research output: Contribution to journalArticle

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