Structural determination of Abeta25-35 micelles by molecular dynamics simulations.

Biophysical Journal
Xiang YuJie Zheng

Abstract

Amyloid-beta (Abeta) peptides and other amyloidogenic proteins can form a wide range of soluble oligomers of varied morphologies at the early aggregation stage, and some of these oligomers are biologically relevant to the pathogenesis of Alzheimer's disease. Spherical micelle-like oligomers have been often observed for many different types of amyloids. Here, we report a hybrid computational approach to systematically construct, search, optimize, and rank soluble micelle-like Abeta25-35 structures with different side-chain packings at the atomic level. Simulations reveal for the first time, to our knowledge, that two Abeta micelles with antiparallel peptide organization and distinct surface hydrophobicity display high structural stability. Stable micelles experience a slow secondary structural transition from turn to alpha-helix. Energetic analysis coupled with computational mutagenesis reveals that van der Waals and solvation energies play a more pronounced role in stabilizing the micelles, whereas the electrostatic energies present a stable but minor energetic contribution to peptide assemblies. Modeled Abeta micelles with shapes and dimensions similar to those of experimentally derived spherical structures also provide detail...Continue Reading

References

Dec 1, 1995·Proteins·D Frishman, P Argos
May 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·W A HouryH A Scheraga
Sep 10, 2003·Journal of Computational Chemistry·Wonpil ImCharles L Brooks
Aug 6, 2004·Journal of Medicinal Chemistry·Anna M D'UrsiDelia Picone
Nov 10, 2004·Proceedings of the National Academy of Sciences of the United States of America·Hung D Nguyen, Carol K Hall
Nov 24, 2004·Biochimie·Mireille Dumoulin, Christopher M Dobson
Jun 28, 2005·Nucleic Acids Research·Dina Schneidman-DuhovnyHaim J Wolfson
Nov 29, 2005·Journal of Chemical Information and Modeling·A KarsaiM S Z Kellermayer
Jun 13, 2006·Biophysical Journal·Guanghong Wei, Joan-Emma Shea
Jul 21, 2006·The Journal of Physical Chemistry. B·Raimon Sabaté, Joan Estelrich
Nov 30, 2006·Journal of Peptide Science : an Official Publication of the European Peptide Society·Cinzia EspositoAnna Maria D'ursi
Apr 22, 2008·Nucleic Acids Research·Efrat MashiachHaim J Wolfson
May 27, 2008·Neurotoxicology·Eun Cheng SuhKyung Eun Lee
Jul 30, 2008·Journal of the American Chemical Society·Mary Griffin KroneJoan-Emma Shea
Aug 30, 2008·The Journal of Biological Chemistry·Charles G Glabe
Dec 23, 2008·The Journal of Biological Chemistry·Rakez KayedCharles Glabe
Jan 10, 2009·The Journal of Physical Chemistry. B·Smita MukherjeeFeng Gai
Jun 3, 2009·Biophysical Journal·Takako Takeda, Dmitri K Klimov
Jul 8, 2009·Proceedings of the National Academy of Sciences of the United States of America·Govardhan ReddyD Thirumalai
Dec 18, 2009·The Journal of Physical Chemistry. B·Jie ZhengQiuming Wang

❮ Previous
Next ❯

Citations

Jun 21, 2011·PloS One·Xiang Yu, Jie Zheng
Dec 3, 2015·ACS Chemical Neuroscience·Natália E C de AlmeidaMichael T Bowers
Aug 11, 2015·ACS Chemical Neuroscience·Rundong HuJie Zheng
Oct 27, 2016·The Journal of Chemical Physics·Size ZhengMuhammad Sahimi
Aug 19, 2015·Physical Chemistry Chemical Physics : PCCP·Mingzhen ZhangJie Zheng
Jul 28, 2012·Chemical Communications : Chem Comm·Wen LiMyongsoo Lee
Mar 3, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yanxian ZhangJie Zheng

❮ Previous
Next ❯

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.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.