Concerted conformational exchange processes in molecular adducts of antimony pentachloride and N,N′-alkylureas

Tetrahedron ◽  
1971 ◽  
Vol 27 (19) ◽  
pp. 4583-4591 ◽  
Author(s):  
G. Olofsson ◽  
P. Stilbs ◽  
T. Drakenberg ◽  
S. Forsén
Keyword(s):  
Conformational Exchange ◽  
Antimony Pentachloride ◽  
Exchange Processes ◽  
Molecular Adducts

scholarly journals Structural ensembles based on NMR parameters suggest a complex pathway of ligand binding in human gastrotropin

2018 ◽  
Author(s):  
Zita Harmat ◽  
András L. Szabó ◽  
Orsolya Toke ◽  
Zoltán Gáspári
Keyword(s):  
Bile Salts ◽  
Conformational Exchange ◽  
Internal Cavity ◽  
Dynamic Nmr ◽  
Nmr Parameters ◽  
Exchange Processes ◽  
Second Mode ◽  
Structural Ensembles ◽  
Partial Unfolding ◽  
Dynamics Simulations

AbstractGastrotropin, the intracellular carrier of bile salts in the small intestine, binds two ligand molecules simultaneously in its internal cavity. The molecular rearrangements required for ligand entry are not yet fully clear. To improve our understanding of the binding process we combined molecular dynamics simulations with available structural and dynamic NMR parameters. The resulting ensembles reveal two distinct modes of barrel opening with one corresponding to the transition between the apo and holo states, whereas the other affecting different protein regions in both ligation states. Comparison of the calculated structures with NMR-derived parameters reporting on slow conformational exchange processes suggests that the protein undergoes partial unfolding along a path related to the second mode of the identified barrel opening motion.

scholarly journals Analysis of Conformational Exchange Processes using Methyl-TROSY-Based Hahn Echo Measurements of Quadruple-Quantum Relaxation

2021 ◽  
Author(s):  
Christopher Andrew Waudby ◽  
John Christodoulou
Keyword(s):  
Chemical Shift ◽  
Chemical Exchange ◽  
Relaxation Dispersion ◽  
Conformational Exchange ◽  
Parameter Estimates ◽  
Relaxation Rates ◽  
Exchange Processes ◽  
Methyl Trosy ◽  
Quantum Transitions ◽  
Order Of Magnitude

Abstract. Transverse nuclear spin relaxation is a sensitive probe of chemical exchange on timescales on the order of microseconds to milliseconds. Here we present an experiment for the simultaneous measurement of the relaxation rates of two quadruple-quantum transitions in 13CH3-labelled methyl groups. These coherences are protected against relaxation by intra-methyl dipolar interactions, and so have unexpectedly long lifetimes within perdeuterated biomacromolecules. However, these coherences also have an order of magnitude higher sensitivity to chemical exchange broadening than lower order coherences, and therefore provide ideal probes of dynamic processes. We show that analysis of the static magnetic field dependence of zero-, double- and quadruple-quantum Hahn echo relaxation rates provides a robust indication of chemical exchange, and can determine the signed relative magnitudes of proton and carbon chemical shift differences between ground and excited states. We also demonstrate that this analysis can be combined with established CPMG relaxation dispersion measurements, providing improved precision in parameter estimates, particularly in the determination of 1H chemical shift differences.

scholarly journals Towards autonomous analysis of Chemical Exchange Saturation Transfer experiments using Deep Neural Networks

2021 ◽  
Author(s):  
Gogulan Karunanithy ◽  
Tairan Yuwen ◽  
Lewis E Kay ◽  
D Flemming Hansen
Keyword(s):  
Neural Networks ◽  
Deep Neural Networks ◽  
Chemical Exchange ◽  
Chemical Shifts ◽  
Conformational Exchange ◽  
Chemical Exchange Saturation Transfer ◽  
Saturation Transfer ◽  
Nmr Data ◽  
Exchange Processes ◽  
Fitting Procedures

Macromolecules often exchange between functional states on timescales that can be accessed with NMR spectroscopy and many NMR tools have been developed to characterise the kinetics and thermodynamics of the exchange processes, as well as the structure of the conformers that are involved. However, analysis of the NMR data that report on exchanging macromolecules often hinges on complex least-squares fitting procedures as well as human experience and intuition, which, in some cases, limits the widespread use of the methods. The applications of deep neural networks (DNNs) and artificial intelligence have increased significantly in the sciences, and recently, specifically, within the field of biomolecular NMR, where DNNs are now available for tasks such as the reconstruction of sparsely sampled spectra, peak picking, and virtual decoupling. Here we present a DNN for the analysis of chemical exchange saturation transfer (CEST) data reporting on two- or three-site chemical exchange involving sparse state lifetimes of between approximately 3 - 60 ms, the range most frequently observed via experiment. The work presented here focuses on the 1H CEST class of methods that are further complicated, in relation to applications to other nuclei, by anti-phase features. The developed DNNs accurately predict the chemical shifts of nuclei in the exchanging species directly from anti-phase 1HN CEST profiles, along with an uncertainty associated with the predictions. The performance of the DNN was quantitatively assessed using both synthetic and experimental anti-phase CEST profiles. The assessments show that the DNN accurately determines chemical shifts and their associated uncertainties. The DNNs developed here do not contain any parameters for the end-user to adjust and the method therefore allows for autonomous analysis of complex NMR data that report on conformational exchange.

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