Microsecond Time-Scale Conformational Exchange in Proteins: Using Long Molecular Dynamics Trajectory To Simulate NMR Relaxation Dispersion Data

2012 ◽  
Vol 134 (5) ◽  
pp. 2555-2562 ◽  
Author(s):  
Yi Xue ◽  
Joshua M. Ward ◽  
Tairan Yuwen ◽  
Ivan S. Podkorytov ◽  
Nikolai R. Skrynnikov
Keyword(s):  
Molecular Dynamics ◽  
Time Scale ◽  
Nmr Relaxation ◽  
Relaxation Dispersion ◽  
Conformational Exchange ◽  
Dispersion Data ◽  
Molecular Dynamics Trajectory

scholarly journals Analysis of Artifacts Caused by Pulse Imperfections in CPMG Pulse Trains in NMR Relaxation Dispersion Experiments

2018 ◽  
Vol 4 (3) ◽  
pp. 33 ◽  
Author(s):  
Tsuyoshi Konuma ◽  
Aritaka Nagadoi ◽  
Jun-ichi Kurita ◽  
Takahisa Ikegami
Keyword(s):  
Dipolar Coupling ◽  
Residual Dipolar Coupling ◽  
Nmr Relaxation ◽  
Relaxation Dispersion ◽  
Conformational Exchange ◽  
Resonance Effects ◽  
Pulse Trains ◽  
At Resonance ◽  
Selective Inversion ◽  
Resonance Relaxation

Nuclear magnetic resonance relaxation dispersion (rd) experiments provide kinetics and thermodynamics information of molecules undergoing conformational exchange. Rd experiments often use a Carr-Purcell-Meiboom-Gill (CPMG) pulse train equally separated by a spin-state selective inversion element (U-element). Even with measurement parameters carefully set, however, parts of 1H–15N correlations sometimes exhibit large artifacts that may hamper the subsequent analyses. We analyzed such artifacts with a combination of NMR measurements and simulation. We found that particularly the lowest CPMG frequency (νcpmg) can also introduce large artifacts into amide 1H–15N and aromatic 1H–13C correlations whose 15N/13C resonances are very close to the carrier frequencies. The simulation showed that the off-resonance effects and miscalibration of the CPMG π pulses generate artifact maxima at resonance offsets of even and odd multiples of νcpmg, respectively. We demonstrate that a method once introduced into the rd experiments for molecules having residual dipolar coupling significantly reduces artifacts. In the method the 15N/13C π pulse phase in the U-element is chosen between x and y. We show that the correctly adjusted sequence is tolerant to miscalibration of the CPMG π pulse power as large as ±10% for most amide 15N and aromatic 13C resonances of proteins.

scholarly journals Searching for Correlated Conformational Dynamics: Analysis of the NMR Relaxation Dispersions with Akaike's Information Theory and Hierarchical Clustering

2017 ◽  
Author(s):  
Evgenii L. Kovrigin
Keyword(s):  
Conformational Dynamics ◽  
Nmr Relaxation ◽  
Hierarchical Cluster ◽  
Information Criteria ◽  
Relaxation Dispersion ◽  
Spin Groups ◽  
Dispersion Data ◽  
Poorly Soluble ◽  
The Difference ◽  
Best Fit

ABSTRACT:In this manuscript, I am proposing an approach for identification of correlated exchange in proteins via analysis of the NMR relaxation dispersion data. For a set of spins experiencing exchange, every relaxation dispersion datasets is fit individually and then—globally while paired with every other dataset. The corrected Akaike’ s Information Criteria (AICc) for individual and global fits are used to evaluate the likelihood of two spins to report on the same dynamic event. Application of hierarchical cluster analysis reveals correlated spin groups using the difference in AICcs as a measure of similarity within the pairs. This approach to detection of correlated dynamics is independent of accuracy of best-fit parameters rendering it less sensitive to experimental noise. High throughput and the absence of the operator bias might make it applicable to a relatively lower quality NMR relaxation dispersion data from large and poorly soluble systems.

scholarly journals relax: the analysis of biomolecular kinetics and thermodynamics using NMR relaxation dispersion data

2014 ◽  
Vol 30 (15) ◽  
pp. 2219-2220 ◽  
Author(s):  
Sébastien Morin ◽  
Troels E Linnet ◽  
Mathilde Lescanne ◽  
Paul Schanda ◽  
Gary S Thompson ◽  
...  
Keyword(s):  
Nmr Relaxation ◽  
Relaxation Dispersion ◽  
Kinetics And Thermodynamics ◽  
Dispersion Data

scholarly journals Atomistic picture of conformational exchange in a T4 lysozyme cavity mutant: an experiment-guided molecular dynamics study

2016 ◽  
Vol 7 (6) ◽  
pp. 3602-3613 ◽  
Author(s):  
Pramodh Vallurupalli ◽  
Nilmadhab Chakrabarti ◽  
Régis Pomès ◽  
Lewis E. Kay
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Relaxation Dispersion ◽  
Conformational Exchange ◽  
T4 Lysozyme ◽  
Nmr Techniques ◽  
Relaxation Dispersion Nmr ◽  
Dynamics Simulations

Relaxation-dispersion NMR techniques and molecular dynamics simulations have been used to understand how a cavity mutant of T4 lysozyme interconverts between two compact conformations.

scholarly journals relax: the analysis of biomolecular kinetics and thermodynamics using NMR relaxation dispersion data

2019 ◽  
Vol 35 (20) ◽  
pp. 4205-4205
Author(s):  
Sébastien Morin ◽  
Troels E Linnet ◽  
Mathilde Lescanne ◽  
Paul Schanda ◽  
Gary S Thompson ◽  
...  
Keyword(s):  
Nmr Relaxation ◽  
Relaxation Dispersion ◽  
Kinetics And Thermodynamics ◽  
Dispersion Data

scholarly journals Mapping transiently formed and sparsely populated conformations on a complex energy landscape

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Yong Wang ◽  
Elena Papaleo ◽  
Kresten Lindorff-Larsen
Keyword(s):  
Energy Landscape ◽  
Nmr Relaxation ◽  
Relaxation Dispersion ◽  
Conformational Exchange ◽  
Internal Cavity ◽  
T4 Lysozyme ◽  
Enhanced Sampling ◽  
Exchange Processes ◽  
Dynamics Simulations ◽  
A Minor

Determining the structures, kinetics, thermodynamics and mechanisms that underlie conformational exchange processes in proteins remains extremely difficult. Only in favourable cases is it possible to provide atomic-level descriptions of sparsely populated and transiently formed alternative conformations. Here we benchmark the ability of enhanced-sampling molecular dynamics simulations to determine the free energy landscape of the L99A cavity mutant of T4 lysozyme. We find that the simulations capture key properties previously measured by NMR relaxation dispersion methods including the structure of a minor conformation, the kinetics and thermodynamics of conformational exchange, and the effect of mutations. We discover a new tunnel that involves the transient exposure towards the solvent of an internal cavity, and show it to be relevant for ligand escape. Together, our results provide a comprehensive view of the structural landscape of a protein, and point forward to studies of conformational exchange in systems that are less characterized experimentally.

scholarly journals Automated NMR relaxation dispersion data analysis using NESSY

2011 ◽  
Vol 12 (1) ◽  
Author(s):  
Michael Bieri ◽  
Paul R Gooley
Keyword(s):  
Data Analysis ◽  
Nmr Relaxation ◽  
Relaxation Dispersion ◽  
Dispersion Data

scholarly journals Slow conformational exchange and overall rocking motion in ubiquitin protein crystals

2017 ◽  
Author(s):  
Vilius Kurauskas ◽  
Sergei A. Izmailov ◽  
Olga N. Rogacheva ◽  
Audrey Hessel ◽  
Isabel Ayala ◽  
...  
Keyword(s):  
Solid State Nmr ◽  
Crystal Packing ◽  
Md Simulations ◽  
Relaxation Dispersion ◽  
Conformational Exchange ◽  
Crystal Forms ◽  
Dispersion Data ◽  
Rocking Motion ◽  
Resonance Relaxation ◽  
Kinetics Of

AbstractProteins perform their functions in solution but their structures are most frequently studied inside crystals. Here we probe how the crystal packing alters microsecond dynamics, using solid-state NMR measurements and multi-microsecond MD simulations of different crystal forms of ubiquitin. In particular, NEar-Rotary-resonance Relaxation Dispersion (NERRD) experiments probe angular backbone motion, while Bloch-McConnell Relaxation Dispersion data report on fluctuations of the local electronic environment. These experiments and simulations reveal that the packing of the protein can significantly alter the thermodynamics and kinetics of local conformational exchange. Moreover, we report small-amplitude reorientational motion of protein molecules in the crystal lattice with a ∼3-5° amplitude on a tens-of-microseconds time scale in one of the crystals, but not in others. An intriguing possibility arises that overall motion is to some extent coupled to local dynamics. Our study highlights the importance of considering the packing when analyzing dynamics of crystalline proteins.

Double- and Zero-Quantum NMR Relaxation Dispersion Experiments Sampling Millisecond Time Scale Dynamics in Proteins

2004 ◽  
Vol 126 (6) ◽  
pp. 1886-1891 ◽  
Author(s):  
Vladislav Yu. Orekhov ◽  
Dmitry M. Korzhnev ◽  
Lewis E. Kay
Keyword(s):  
Time Scale ◽  
Nmr Relaxation ◽  
Relaxation Dispersion ◽  
Millisecond Time Scale

Structure and Dynamics of Spherical and Rodlike Alkyl Ethoxylate Surfactant Micelles Investigated Using NMR Relaxation and Atomistic Molecular Dynamics Simulations

2019 ◽  
Author(s):  
Allison Edwards ◽  
Abdolreza Javidialesaadi ◽  
Katie Weigandt ◽  
George Stan ◽  
Charles Eads
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Nmr Relaxation ◽  
Cross Relaxation ◽  
Relaxation Rates ◽  
Surfactant Micelles ◽  
Cylindrical Micelles ◽  
Spherical Micelles ◽  
Dynamics Simulations ◽  
Relative Motions

We study molecular arrangements and dynamics in alkyl ethoxylate nonionic surfactant micelles by combining high field (600 and 700 MHz) NMR relaxation measurements with large-scale atomistic molecular dynamics simulations. For spherical micelles, but not for cylindrical micelles, cross relaxation rates are positive only for surfactant alkyl tail atoms connected to the hydrophilic head group. All cross relaxation rates are negative for cylindrical micelles. This effect is reproducible either by changing composition (ratios of the nonionic surfactants) or changing temperature of a single surfactant in order to change the micelle shape. We validate the micelle shape by SANS and use the results as a guide for our simulations. We calculate parameters that determine relaxation rates directly from simulated trajectories, without introducing specific functional forms. Results indicate that relative motions of nearby atoms are liquid-like, in agreement with 13C T1 measurements, though constrained by micelle morphology. Relative motions of distant atoms have slower components because the relative changes in distances and angles are smaller when the moving atoms are further apart. The slow, long-range motions appear to be responsible for the predominantly negative cross relaxation rates observed in NOESY spectra. The densities of atoms from positions 1 and 2 in the boundary region are lower in spherical micelles compared to cylindrical micelles. Correspondingly, motions in this region are less constrained by micelle morphology in the spherical compared to the cylindrical cases. The two effects of morphology lead to the unusual occurrence of positive cross relaxation involving positions 1 and 2 for spheres.

Sign in / Sign up

Export Citation Format

Share Document