Abstract
NMR spectroscopy is the leading technique to characterize protein internal dynamics at the atomic level and on multiple time scales. However, the structural interpretation of the observables obtained by various measurements is not always straightforward and in many cases dynamics-related parameters are only used to “decorate” static structural models without offering explicit description of conformational heterogeneity. To overcome such limitations, several computational techniques have been developed to generate ensemble-based representations of protein structure and dynamics with the use of NMR-derived data. An important common aspect of the methods is that NMR observables and derived parameters are interpreted as properties of the ensemble instead of individual conformers. The resulting ensembles reflect the experimentally determined internal mobility of proteins at a given time scale and can be used to understand the role of internal motions in biological processes at atomic detail. In this review we provide an overview of the calculation methods currently available and examples of biological insights obtained by the ensemble-based models of the proteins investigated.
Highlights
Nuclear magnetic resonance spectroscopy is the method of choice for structural investigation of proteins and peptides in solution
We argue that the resulting ensembles are better models of protein structures than “static” ones and provide examples of conclusions that could be drawn with the use of ensemble representations
The robustness of the ensemble description is commonly assessed by cross-validation, correspondence to data not used in the generation process
Summary
Nuclear magnetic resonance spectroscopy is the method of choice for structural investigation of proteins and peptides in solution. The dynamic nature of proteins was recognized long before the first dynamics measurements, results obtained with NMR spectroscopy led to the emergence of the current paradigm of protein action where internal dynamics is a key factor in determining and tuning molecular function [2,3]. Despite this dynamics-based view, structural representations of proteins where a single conformer or a number of highly similar ones are shown and used for biological interpretations are still prevalent. Such ensembles can successfully be used to understand biochemical mechanisms at the atomic level [5]
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