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Structural and pathway complexity of β-strand reorganization within aggregates of human transthyretin(105-115) peptide

Document Type

Article

Abstract

Interstrand conformational rearrangements of human transthyretin peptide (TTR(105-115)) within dimeric aggregates were simulated by means of molecular dynamics (MD) with implicit solvation model for a total length of 48 μs. The conformations sampled in the MD simulations were clustered to identify free energy minima without any projections of free energy surface. A connected graph was constructed with nodes (=clusters) and edges corresponding to free energy minima and transitions between nodes, respectively. This connected graph which reflects the complexity of the free energy surface was used to extract the transition disconnectivity graph, which reflects the overall free energy barriers between pairs of free energy minima but does not contain information on transition paths. The routes of transitions between important free energy minima were obtained by further processing the original graph and the MD data. We have found that both parallel and antiparallel aggregates are populated. The parallel aggregates with different alignment patterns are separated by nonnegligible free energy barriers. Multiroutes exist in the interstrand conformational reorganization. Most visited routes do not dominant the kinetics, while less visited routes contribute a little each but they are numerous and their total contributions are actually dominant. There are various kinds of reptation motions, including those through a β-bulge, side-chain aided reptation, and flipping or rotation of a hairpin formed by one strand. © 2007 American Chemical Society.

Publication Title

Journal of Physical Chemistry B

Publication Date

2007

Volume

111

Issue

19

First Page

5425

Last Page

5433

ISSN

1520-6106

DOI

10.1021/jp0703051

APA Citation

Li, D. W., Han, L., & Huo, S. (2007). Structural and Pathway Complexity of β-Strand Reorganization within Aggregates of Human Transthyretin (105− 115) Peptide. The Journal of Physical Chemistry B, 111(19), 5425-5433.

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