Revealing Hidden Helix Propensity in A尾 Peptides by Molecular Dynamics Simulations

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• 作者：Christopher Lockhart ; Dmitri K. Klimov
• 刊名：Journal of Physical Chemistry B
• 出版年：2013
• 出版时间：October 10, 2013
• 年：2013
• 卷：117
• 期：40
• 页码：12030-12038
• 全文大小：437K
• 年卷期：v.117,no.40(October 10, 2013)
• ISSN：1520-5207

文摘

Using all-atom explicit solvent model and exhaustive replica exchange molecular dynamics simulations we studied the conformational ensembles of several amino-truncated A尾 peptides. In our simulations we specifically monitored the formation of helix structure in the C-terminals of various A尾 fragments. We show that the equilibrium distributions of structures adopted by A尾23鈥?0 and A尾10鈥?0 are similar, but sharply distinct from the conformational ensemble of A尾29鈥?0. The latter features a stable helical structure not present in longer fragments. Because the 位-expansion method applied to A尾23鈥?0 identified Lys28 as the residue producing the strongest impact on the C-terminal helix structure, we hypothesized that addition of a single Lys28 to A尾29鈥?0 would change the peptide鈥檚 conformational ensemble. REMD simulations of A尾28鈥?0 confirmed this expectation by showing that in this peptide the helix conformation is destabilized and it adopts structures similar to those of A尾23鈥?0 and A尾10鈥?0. Therefore, a major conformational switch in the A尾 C-terminal occurs by truncating A尾 peptide after the position Lys28. By comparing our findings with previous studies we argue that A尾 C-terminal harbors helical propensity, which can be revealed by various factors, including environment, ligand binding, or sequence truncation.