scholarly journals Determining Sequence-Dependent DNA Oligonucleotide Hybridization and Dehybridization Mechanisms Using Coarse-Grained Molecular Simulation, Markov State Models, and Infrared Spectroscopy

2021 ◽  
Author(s):  
Michael S. Jones ◽  
Brennan Ashwood ◽  
Andrei Tokmakoff ◽  
Andrew L. Ferguson
Keyword(s):  
Infrared Spectroscopy ◽  
Molecular Simulation ◽  
Coarse Grained ◽  
Markov State ◽  
Markov State Models ◽  
Sequence Dependent ◽  
Oligonucleotide Hybridization ◽  
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.

scholarly journals Characterization of Coarse-Grained Helix-Coil Transition Kinetics using Markov State Models

2017 ◽  
Vol 112 (3) ◽  
pp. 194a ◽  
Author(s):  
Joseph F. Rudzinski ◽  
Kurt Kremer ◽  
Tristan Bereau
Keyword(s):  
Coarse Grained ◽  
Markov State ◽  
Markov State Models ◽  
Coil Transition ◽  
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.

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