Structure and dynamics of an unfolded protein examined by molecular dynamics simulation

Journal of the American Chemical Society
Kresten Lindorff-LarsenDavid E Shaw

Abstract

The accurate characterization of the structure and dynamics of proteins in disordered states is a difficult problem at the frontier of structural biology whose solution promises to further our understanding of protein folding and intrinsically disordered proteins. Molecular dynamics (MD) simulations have added considerably to our understanding of folded proteins, but the accuracy with which the force fields used in such simulations can describe disordered proteins is unclear. In this work, using a modern force field, we performed a 200 μs unrestrained MD simulation of the acid-unfolded state of an experimentally well-characterized protein, ACBP, to explore the extent to which state-of-the-art simulation can describe the structural and dynamical features of a disordered protein. By comparing the simulation results with the results of NMR experiments, we demonstrate that the simulation successfully captures important aspects of both the local and global structure. Our simulation was ~2 orders of magnitude longer than those in previous studies of unfolded proteins, a length sufficient to observe repeated formation and breaking of helical structure, which we found to occur on a multimicrosecond time scale. We observed one structura...Continue Reading

References

Dec 1, 1995·Proteins·D Frishman, P Argos
Mar 2, 2002·Science·Judith Klein-SeetharamanHarald Schwalbe
Oct 24, 2002·Journal of the American Chemical Society·Fengli Zhang, Rafael Brüschweiler
Mar 12, 2004·Journal of the American Chemical Society·Kresten Lindorff-LarsenMichele Vendruscolo
Aug 12, 2004·Chemical Reviews·H Jane Dyson, Peter E Wright
Aug 12, 2004·Chemical Reviews·Arthur G Palmer
Feb 3, 2005·Biochemistry·Wolfgang FieberFlemming M Poulsen
Mar 3, 2005·The Journal of Chemical Physics·Yibing ShanDavid E Shaw
Jan 26, 2007·Current Opinion in Structural Biology·Tanja Mittag, Julie D Forman-Kay
Oct 14, 2008·Journal of Biomolecular NMR·Kristofer Modig, Flemming M Poulsen
Jul 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Susanne W BruunFlemming M Poulsen
Apr 26, 2011·Current Opinion in Structural Biology·Peter Tompa
May 5, 2011·Biophysical Journal·Stefano PianaDavid E Shaw
Jul 30, 2011·Science·Greg Miller
Oct 29, 2011·Science·Kresten Lindorff-LarsenDavid E Shaw
Apr 30, 1998·The Journal of Physical Chemistry. B·A D MacKerellM Karplus

❮ Previous
Next ❯

Citations

Sep 17, 2013·Journal of Molecular Graphics & Modelling·Michael Feig, Yuji Sugita
Jul 4, 2012·Journal of the American Chemical Society·Vincent A VoelzVijay S Pande
Apr 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Wenbing HuS Walter Englander
Sep 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yong WangJin Wang
May 24, 2014·PLoS Computational Biology·Drazen Petrov, Bojan Zagrovic
Dec 24, 2013·The Journal of Chemical Physics·Somedatta Pal, Sanjoy Bandyopadhyay
Jan 21, 2014·The Journal of Chemical Physics·Andrey KrokhotinHarold A Scheraga
Apr 5, 2014·The Journal of Chemical Physics·H Wiebe, N Weinberg
May 31, 2014·Proceedings of the National Academy of Sciences of the United States of America·Yong WangJin Wang
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·René WuttkeBenjamin Schuler
Jul 9, 2014·Proceedings of the National Academy of Sciences of the United States of America·R Paul NobregaC Robert Matthews
Jan 10, 2013·Biochimica Et Biophysica Acta·Katja Ostermeir, Martin Zacharias
Oct 29, 2014·Nature Communications·Nathaniel StanleyGianni De Fabritiis
Jan 6, 2016·Cell Communication and Signaling : CCS·Diana M Mitrea, Richard W Kriwacki
Nov 10, 2015·Expert Opinion on Drug Discovery·Susmitha Ambadipudi, Markus Zweckstetter
Jan 23, 2016·The Journal of Physical Chemistry. B·Elio A CinoMikko Karttunen
Mar 31, 2015·Progress in Biophysics and Molecular Biology·Nathaniel StanleyGianni De Fabritiis
Nov 13, 2015·The Journal of Physical Chemistry. B·David Jacob RosenmanAngel E Garcia
Apr 3, 2013·Current Opinion in Structural Biology·Malene Ringkjøbing JensenMartin Blackledge
Mar 8, 2013·Current Opinion in Structural Biology·Domenico Cozzetto, David T Jones
Jun 20, 2015·Protein Science : a Publication of the Protein Society·Gi-Moon Nam, Dmitrii E Makarov
Nov 18, 2015·Journal of Chemical Theory and Computation·Sarah RauscherHelmut Grubmüller
Mar 13, 2015·Protein Science : a Publication of the Protein Society·Yiming Xiao, Lars Konermann
Oct 27, 2015·The Journal of Physical Chemistry. B·Gül H ZerzeJeetain Mittal
Oct 5, 2015·Journal of Biomolecular NMR·Vytautas GapsysMarkus Zweckstetter
Jul 2, 2015·The Journal of Physical Chemistry. B·Divya Nayar, Charusita Chakravarty
Nov 12, 2013·Journal of Molecular Biology·Valéry OzenneJens Danielsson
Jul 31, 2013·Biochimica Et Biophysica Acta·Gaetano InvernizziElena Papaleo
Sep 25, 2012·Current Opinion in Structural Biology·Joseph A MarshJulie D Forman-Kay
Oct 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·John J SkinnerTobin R Sosnick
Sep 6, 2012·Biophysical Journal·Anurag SethiS Gnanakaran
Feb 2, 2015·The Journal of Chemical Physics·Jianfeng HeAntti J Niemi
Apr 27, 2016·Journal of the American Chemical Society·Anton AbyzovMartin Blackledge
Jul 30, 2015·PloS One·Kyle Quynn HoffmannJuan J de Pablo

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.