Mechanism for the α-helix to β-hairpin transition

Feng Ding, Jose M. Borreguero, Sergey V. Buldyrey, H. Eugene Stanley, Nikolay V. Dokholyan

Research output: Contribution to journalArticle

182 Citations (Scopus)

Abstract

The aggregation of α-helix-rich proteins into β-sheet-rich amyloid fibrils is associated with fatal diseases, such as Alzheimer's disease and prion disease. During an aggregation process, protein secondary structure elements-α-helices-undergo conformational changes to α-sheets. The fact that proteins with different sequences and structures undergo a similar transition on aggregation suggests that the sequence nonspecific hydrogen bond interaction among protein backbones is an important factor. We perform molecular dynamics simulations of a polyalanine model, which is an α-helix in its native state and observe a metastable β-hairpin intermediate. Although a β-hairpin has larger potential energy than an α-helix, the entropy of a β-hairpin is larger because of fewer constraints imposed by the hydrogen bonds. In the vicinity of the transition temperature, we observe the interconversion of the α-helix and β-sheet states via a random coil state. We also study the effect of the environment by varying the relative strength of side-chain interactions for a designed peptide-an α-helix in its native state. For a certain range of side-chain interaction strengths, we find that the intermediate β-hairpin state is destabilized and even disappears, suggesting an important role of the environment in the aggregation propensity of a peptide.

Original languageEnglish (US)
Pages (from-to)220-228
Number of pages9
JournalProteins: Structure, Function and Genetics
Volume53
Issue number2
DOIs
StatePublished - Nov 1 2003

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Agglomeration
Hydrogen
Hydrogen bonds
Peptides
Proteins
Prion Diseases
Transition Temperature
Entropy
Molecular Dynamics Simulation
Amyloid
Prions
Alzheimer Disease
Potential energy
Molecular dynamics
Computer simulation
polyalanine
Protein Structural Elements

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Cite this

Ding, Feng ; Borreguero, Jose M. ; Buldyrey, Sergey V. ; Stanley, H. Eugene ; Dokholyan, Nikolay V. / Mechanism for the α-helix to β-hairpin transition. In: Proteins: Structure, Function and Genetics. 2003 ; Vol. 53, No. 2. pp. 220-228.
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Mechanism for the α-helix to β-hairpin transition. / Ding, Feng; Borreguero, Jose M.; Buldyrey, Sergey V.; Stanley, H. Eugene; Dokholyan, Nikolay V.

In: Proteins: Structure, Function and Genetics, Vol. 53, No. 2, 01.11.2003, p. 220-228.

Research output: Contribution to journalArticle

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