[NMR paper] Mechanistic models of chemical exchange induced relaxation in protein NMR.

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Mechanistic models of chemical exchange induced relaxation in protein NMR.

Related Articles Mechanistic models of chemical exchange induced relaxation in protein NMR.

J Am Chem Soc. 2016 Dec 13;

Authors: Olsson S, Noé F

Abstract
Long-lived conformational states and their interconversion rates critically determine protein function and regulation. When these states have distinct chemical shifts the measurement of relaxation by NMR may provide us with useful information about their structure, kinetics and thermodynamics at atomic resolution. However, as these experimental data are sensitive to many structural and dynamic effects, their interpretation with phenomenological models is challenging, even if only a few meta-stable states are involved. Consequently, experiment specific approximations and simplifications must often be used at the cost of a modest interpretation of the data. Here, we show how molecular dynamics simulations analyzed through Markov state models (MSM) and the related hidden Markov state models (HMSM) may be used to establish mechanistic models that provide a microscopic interpretation of NMR relaxation data. Using ubiquitin and BPTI as examples we demonstrate how the approach allows us to dissect experimental data into a number of dynamic processes between meta-stable states. Such a microscopic view may greatly facilitate the mechanistic interpretation of experimental data, and serve as a next-generation method for the validation of molecular mechanics force fields and chemical shift prediction algorithms.


PMID: 27958728 [PubMed - as supplied by publisher]



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