Motional clustering in supra-τ; c; conformational exchange influences NOE cross-relaxation rate

Kolloff, Christopher and Mazur, Adam and Marzinek, Jan K. and Bond, Peter J. and Olsson, Simon and Hiller, Sebastian. (2022) Motional clustering in supra-τ; c; conformational exchange influences NOE cross-relaxation rate. Journal of Magnetic Resonance, 338. p. 107196.

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Official URL: https://edoc.unibas.ch/91290/

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Biomolecular spin relaxation processes, such as the NOE, are commonly modeled by rotational τ; c; -tumbling combined with fast motions on the sub-τ; c; timescale. Motions on the supra-τ; c; timescale, in contrast, are considered to be completely decorrelated to the molecular tumbling and therefore invisible. Here, we show how supra-τ; c; dynamics can nonetheless influence the NOE build-up between methyl groups. This effect arises because supra-τ; c; motions can cluster the fast-motion ensembles into discrete states, affecting distance averaging as well as the fast-motion order parameter and hence the cross-relaxation rate. We present a computational approach to estimate methyl-methyl cross-relaxation rates from extensive (>100×τ; c; ) all-atom molecular dynamics (MD) trajectories on the example of the 723-residue protein Malate Synthase G. The approach uses Markov state models (MSMs) to resolve transitions between metastable states and thus to discriminate between sub-τ; c; and supra-τ; c; conformational exchange. We find that supra-τ; c; exchange typically increases NOESY cross-peak intensities. The methods described in this work extend the theory of modeling sub-μs dynamics in spin relaxation and thus contribute to a quantitative estimation of NOE cross-relaxation rates from MD simulations, eventually leading to increased precision in structural and functional studies of large proteins.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Research IT (Podvinec)
UniBasel Contributors:Mazur, Adam and Hiller, Sebastian and Kolloff, Christopher
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:13 Dec 2022 14:54
Deposited On:13 Dec 2022 14:54

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