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Mechanism for the α‐helix to β‐hairpin transition
Author(s) -
Ding Feng,
Borreguero Jose M.,
Buldyrey Sergey V.,
Stanley H. Eugene,
Dokholyan Nikolay V.
Publication year - 2003
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10468
Subject(s) - random coil , helix (gastropod) , alpha helix , chemistry , hydrogen bond , beta sheet , molecular dynamics , crystallography , biophysics , protein secondary structure , protein structure , peptide , metastability , amyloid beta , circular dichroism , biochemistry , biology , molecule , computational chemistry , ecology , organic chemistry , snail
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 β‐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. Proteins 2003. © 2003 Wiley‐Liss, Inc.