scholarly journals Reconciling Simulated Ensembles of Apomyoglobin with Experimental Hydrogen/Deuterium Exchange Data Using Bayesian Inference and Multiensemble Markov State Models

2020 ◽  
Vol 16 (2) ◽  
pp. 1333-1348 ◽  
Author(s):  
Hongbin Wan ◽  
Yunhui Ge ◽  
Asghar Razavi ◽  
Vincent A. Voelz
Keyword(s):  
Bayesian Inference ◽  
Deuterium Exchange ◽  
Hydrogen Deuterium Exchange ◽  
Markov State ◽  
Markov State Models ◽  
Hydrogen Deuterium ◽  
State Models ◽  
Exchange Data

scholarly journals HD-eXplosion: visualization of hydrogen–deuterium exchange data as chiclet and volcano plots with statistical filtering

2020 ◽  
Author(s):  
Naifu Zhang ◽  
Xiaohe Yu ◽  
Xinchao Zhang ◽  
Sheena D’Arcy
Keyword(s):  
Source Code ◽  
Deuterium Exchange ◽  
Hydrogen Deuterium Exchange ◽  
Web Based ◽  
Data Presentation ◽  
Software Packages ◽  
Volcano Plots ◽  
Hydrogen Deuterium ◽  
Exchange Data ◽  
Publication Quality

Abstract Summary Hydrogen–Deuterium eXchange coupled to mass spectrometry is a powerful tool for the analysis of protein dynamics and interactions. Bottom-up experiments looking at deuterium uptake differences between various conditions are the most common. These produce multi-dimensional data that can be challenging to depict in a single visual format. Each user must also set significance thresholds to define meaningful differences and make these apparent in data presentation. To assist in this process, we have created HD-eXplosion, an open-source, web-based application for the generation of chiclet and volcano plots with statistical filters. HD-eXplosion fills a void in available software packages and produces customizable plots that are publication quality. Availability and implementation The HD-eXplosion application is available at http://hd-explosion.utdallas.edu. The source code can be found at https://github.com/HD-Explosion.

scholarly journals Reconciling simulated ensembles of apomyoglobin with experimental HDX data using Bayesian inference and multi-ensemble Markov State Models

2019 ◽  
Author(s):  
Hongbin Wan ◽  
Yunhui Ge ◽  
Asghar Razavi ◽  
Vincent A. Voelz
Keyword(s):  
Molecular Dynamics ◽  
Bayesian Inference ◽  
Conformational Dynamics ◽  
Molecular Simulations ◽  
Dynamics Simulation ◽  
Trajectory Data ◽  
Protection Factor ◽  
Markov State ◽  
Markov State Models ◽  
State Models

AbstractHydrogen/deuterium exchange (HDX) is a powerful technique to investigate protein conformational dynamics at amino acid resolution. Because HDX provides a measurement of solvent exposure of backbone hydrogens, ensemble-averaged over potentially slow kinetic processes, it has been challenging to use HDX protection factors to refine structural ensembles obtained from molecular dynamics simulations. This entails two dual challenges: (1) identifying structural observables that best correlate with backbone amide protection from exchange, and (2) restraining these observables in molecular simulations to model ensembles consistent with experimental measurements. Here, we make significant progress on both fronts. First, we describe an improved predictor of HDX protection factors from structural observables in simulated ensembles, parameterized from ultra-long molecular dynamics simulation trajectory data, with a Bayesian inference approach used to retain the full posterior distribution of model parameters.We next present a new method for obtaining simulated ensembles in agreement with experimental HDX protection factors, in which molecular simulations are performed at various temperatures and restraint biases, and used to construct multi-ensemble Markov State Models (MSMs). Finally, the BICePs algorithm (Bayesian Inference of Conformational Populations) is then used with our HDX protection factor predictor to infer which thermodynamic ensemble agrees best with experiment, and estimate populations of each conformational state in the MSM. To illustrate the approach, we use a combination of HDX protection factor restraints and chemical shift restraints to model the conformational ensemble of apomyoglobin at pH 6. The resulting ensemble agrees well with experiment, and gives insight into the all-atom structure of disordered helices F and H in the absence of heme.Graphical TOC Entry

scholarly journals Start2Fold: a database of hydrogen/deuterium exchange data on protein folding and stability

2015 ◽  
Vol 44 (D1) ◽  
pp. D429-D434 ◽  
Author(s):  
Rita Pancsa ◽  
Mihaly Varadi ◽  
Peter Tompa ◽  
Wim F. Vranken
Keyword(s):  
Protein Folding ◽  
Deuterium Exchange ◽  
Hydrogen Deuterium Exchange ◽  
Hydrogen Deuterium ◽  
Exchange Data

scholarly journals Methods for the analysis of high precision differential hydrogen–deuterium exchange data

2011 ◽  
Vol 302 (1-3) ◽  
pp. 59-68 ◽  
Author(s):  
Michael J. Chalmers ◽  
Bruce D. Pascal ◽  
Scooter Willis ◽  
Jun Zhang ◽  
Stephen J. Iturria ◽  
...  
Keyword(s):  
High Precision ◽  
Deuterium Exchange ◽  
Hydrogen Deuterium Exchange ◽  
Hydrogen Deuterium ◽  
Exchange Data

Improving Spectral Validation Rates in Hydrogen–Deuterium Exchange Data Analysis

2021 ◽  
Author(s):  
Shaunak Raval ◽  
Vladimir Sarpe ◽  
Morgan Hepburn ◽  
D. Alex Crowder ◽  
Terry Zhang ◽  
...  
Keyword(s):  
Data Analysis ◽  
Deuterium Exchange ◽  
Hydrogen Deuterium Exchange ◽  
Hydrogen Deuterium ◽  
Exchange Data

Probing the Nature of the Blue-Shifted Intermediate of Photoactive Yellow Protein in Solution by NMR:  Hydrogen−Deuterium Exchange Data and pH Studies†

Biochemistry ◽  
2000 ◽  
Vol 39 (47) ◽  
pp. 14392-14399 ◽  
Author(s):  
C. Jeremy Craven ◽  
Nocky M. Derix ◽  
Johnny Hendriks ◽  
Rolf Boelens ◽  
Klaas J. Hellingwerf ◽  
...  
Keyword(s):  
Deuterium Exchange ◽  
Photoactive Yellow Protein ◽  
Hydrogen Deuterium Exchange ◽  
Hydrogen Deuterium ◽  
Exchange Data
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