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Assessing and refining molecular dynamics simulations of proteins with nuclear magnetic resonance data

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Abstract

The sophistication of the force fields, algorithms and hardware used for molecular dynamics (MD) simulations of proteins is continuously increasing. No matter how advanced the methodology, however, it is essential to evaluate the appropriateness of the structures sampled in a simulation by comparison with quantitative experimental data. Solution nuclear magnetic resonance (NMR) data are particularly useful for checking the quality of protein simulations, as they provide both structural and dynamic information on a variety of temporal and spatial scales. Here, various features and implications of using NMR data to validate and bias MD simulations are outlined, including an overview of the different types of NMR data that report directly on structural properties and of relevant simulation techniques. The focus throughout is on how to properly account for conformational averaging, particularly within the context of the assumptions inherent in the relationships that link NMR data to structural properties.

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Acknowledgements

I thank the very many people with whom I have discussed the issues involved in combining NMR data with MD simulations, in particular, Prof. Wilfred van Gunsteren, to whom this article is dedicated on the occasion of his 65th birthday.

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  1. Centre for Theoretical Chemistry and Physics, Institute of Natural Sciences, Massey University Albany, Albany Highway, Auckland, 0632, New Zealand

    Jane R. Allison

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Allison, J.R. Assessing and refining molecular dynamics simulations of proteins with nuclear magnetic resonance data. Biophys Rev 4, 189–203 (2012). https://doi.org/10.1007/s12551-012-0087-6

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