Faculty Opinions recommendation of Constructing Markov State Models to elucidate the functional conformational changes of complex biomolecules.

2017 ◽  
Author(s):  
Qiang Cui
Keyword(s):  
Conformational Changes ◽  
Markov State ◽  
Markov State Models ◽  
State Models

scholarly journals Membrane Interactions of α-Synuclein Revealed by Multiscale Molecular Dynamics Simulations, Markov State Models, and NMR

2020 ◽  
Author(s):  
Sarah-Beth T. A. Amos ◽  
Thomas C. Schwarz ◽  
Jiye Shi ◽  
Benjamin P. Cossins ◽  
Terry S. Baker ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Lipid Bilayers ◽  
Conformational Changes ◽  
Cell Damage ◽  
Lipid Binding ◽  
Coarse Grained ◽  
Mixed Composition ◽  
Markov State ◽  
Markov State Models ◽  
State Models

Abstractα-Synuclein is a presynaptic protein that binds to cell membranes and is linked to Parkinson’s disease (PD). Whilst the normal function of remains α-synuclein remains uncertain, it is thought that oligomerization of the protein on the cell membrane contributes to cell damage. Knowledge of how α-synuclein binds to lipid bilayers is therefore of great interest as a likely first step in the molecular pathophysiology of PD, and may provide insight of the phenotype of PD-promoting mutations. We use coarse-grained and atomistic simulations in conjunction with NMR and cross-linking mass spectrometry studies of α-synuclein bound to anionic lipid bilayers to reveal a break in the helical structure of the NAC region, which may give rise to subsequent oligomer formation. Coarse-grained simulations of α-synuclein show that the interhelical region leads recognition and binding to both POPG and mixed composition bilayers and identifies important protein-lipid contacts, including those in the region between the two helices in the folded structure. We extend these simulations with all-atom simulations of the initial binding event to reveal details of the time-progression of lipid binding. We present secondary structure analysis that reveals points of possible β-strand formation in the structure, and investigate intramolecular contacts with simulations and mass-spectrometry crosslinking. Additionally we show how Markov state models can be used to investigate possible conformational changes of membrane bound α-synuclein in the NAC region, and we extract representative structures. These structural insights will aid the design and development of novel therapeutic approaches.

Elucidating molecular mechanisms of functional conformational changes of proteins via Markov state models

2021 ◽  
Vol 67 ◽  
pp. 69-77
Author(s):  
Xiaowei Wang ◽  
Ilona Christy Unarta ◽  
Peter Pak-Hang Cheung ◽  
Xuhui Huang
Keyword(s):  
Conformational Changes ◽  
Molecular Mechanisms ◽  
Markov State ◽  
Markov State Models ◽  
State Models

scholarly journals Thermodynamics and kinetics of the amyloid-β peptide revealed by Markov state models based on MD data in agreement with experiment

2021 ◽  
Author(s):  
Arghadwip Paul ◽  
Suman Samantray ◽  
Marco Anteghini ◽  
Mohammed Khaled ◽  
Birgit Strodel
Keyword(s):  
Amyloid Β ◽  
Md Simulations ◽  
Amyloid Β Peptide ◽  
Intrinsically Disordered ◽  
Thermodynamics And Kinetics ◽  
Markov State ◽  
Markov State Models ◽  
State Models ◽  
Kinetics Of

The convergence of MD simulations is tested using varying measures for the intrinsically disordered amyloid-β peptide (Aβ). Markov state models show that 20–30 μs of MD is needed to reliably reproduce the thermodynamics and kinetics of Aβ.

scholarly journals Markov State Models Reveal a Two-Step Mechanism of miRNA Loading into the Human Argonaute Protein: Selective Binding followed by Structural Re-arrangement

2015 ◽  
Vol 11 (7) ◽  
pp. e1004404 ◽  
Author(s):  
Hanlun Jiang ◽  
Fu Kit Sheong ◽  
Lizhe Zhu ◽  
Xin Gao ◽  
Julie Bernauer ◽  
...  
Keyword(s):  
Argonaute Protein ◽  
Selective Binding ◽  
Markov State ◽  
Markov State Models ◽  
State Models ◽  
Step Mechanism

scholarly journals Markov state models based on milestoning

2011 ◽  
Vol 134 (20) ◽  
pp. 204105 ◽  
Author(s):  
Christof Schütte ◽  
Frank Noé ◽  
Jianfeng Lu ◽  
Marco Sarich ◽  
Eric Vanden-Eijnden
Keyword(s):  
Markov State ◽  
Markov State Models ◽  
State Models
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