Unfolding of α-helical 20-residue poly-glutamic acid analyzed by multiple runs of canonical molecular dynamics simulations

PeerJ
Naoki OgasawaraTakuya Takahashi

Abstract

Elucidating the molecular mechanism of helix-coil transitions of short peptides is a long-standing conundrum in physical chemistry. Although the helix-coil transitions of poly-glutamic acid (PGA) have been extensively studied, the molecular details of its unfolding process still remain unclear. We performed all-atom canonical molecular dynamics simulations for a 20-residue PGA, over a total of 19 μs, in order to investigate its helix-unfolding processes in atomic resolution. Among the 28 simulations, starting with the α-helical conformation, all showed an unfolding process triggered by the unwinding of terminal residues, rather than by kinking and unwinding of the middle region of the chain. The helix-coil-helix conformation which is speculated by the previous experiments was not observed. Upon comparison between the N- and C-termini, the latter tended to be unstable and easily unfolded. While the probabilities of helix elongation were almost the same among the N-terminal, middle, and C-terminal regions of the chain, unwinding of the helix was enriched at the C-terminal region. The turn and 310-helix conformations were kinetic intermediates in the formation and deformation of α-helix, consistent with the previous computational ...Continue Reading

References

Jan 1, 1981·Advances in Protein Chemistry·J S Richardson
Jun 1, 1995·Biophysical Chemistry·R L Baldwin
Jun 14, 1996·Journal of Molecular Biology·W S Young, C L Brooks
Jun 23, 1999·Proceedings of the National Academy of Sciences of the United States of America·D T ClarkeG R Jones
Sep 26, 2002·Journal of the American Chemical Society·Tetsunari KimuraIsao Morishima
Jan 25, 2005·Biophysical Journal·Eric J Sorin, Vijay S Pande
Jul 20, 2005·Biochimica Et Biophysica Acta·Sharon M KellyNicholas C Price
Jul 21, 2006·The Journal of Physical Chemistry. B·Keiichi InoueMasahide Terazima
Mar 21, 2007·Biopolymers·John M FinkeJay R Winkler
Apr 5, 2007·Nature Protocols·Norma J Greenfield
Jun 29, 2007·Proteins·Yantao ChenJiandong Ding
Jan 18, 2008·Biophysical Journal·Christopher B Stanley, Helmut H Strey
Jul 24, 2013·Proceedings of the National Academy of Sciences of the United States of America·Sabine NeumaierThomas Kiefhaber
Mar 13, 2015·The Journal of Physical Chemistry. B·Stefano PianaDavid E Shaw
Oct 27, 2015·PLoS Computational Biology·Àngel Gómez-SiciliaMariano Carrión-Vázquez
Jan 1, 2014·Biophysics·Zhi-Jie QinHiroshi Kihara
Nov 8, 2016·Nature Methods·Jing HuangAlexander D MacKerell
Dec 8, 2016·Biophysics and Physicobiology·Yu TakanoHaruki Nakamura

❮ Previous
Next ❯

Citations

Mar 18, 2020·The Journal of Physical Chemistry. B·Piotr BatysMaria Sammalkorpi

❮ Previous
Next ❯

Methods Mentioned

BETA
protein folding
circular dichroism
fluorescence resonance
FRET

Software Mentioned

tLEaP
DSSP
Ide
Sim
AMBER

Related Concepts

Related Feeds

Cajal Bodies & Gems

Cajal bodies or coiled bodies are dense foci of coilin protein. Gemini of Cajal bodies, or gems, are microscopically similar to Cajal bodies. It is believed that Cajal bodies play important roles in RNA processing while gems assist the Cajal bodies. Find the latest research on Cajal bodies and gems here.