Patterns in Protein Flexibility: A Comparison of NMR “Ensembles”, MD Trajectories, and Crystallographic B-Factors

• Main Authors: Christopher Reinknecht, Anthony Riga, Jasmin Rivera, David A. Snyder
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Molecules
• Subjects: Friedman’s test; backbone atom coordinate variances and uncertainties; superimposition
• Online Access: https://www.mdpi.com/1420-3049/26/5/1484

Proteins are molecular machines requiring flexibility to function. Crystallographic B-factors and Molecular Dynamics (MD) simulations both provide insights into protein flexibility on an atomic scale. Nuclear Magnetic Resonance (NMR) lacks a universally accepted analog of the B-factor. However, a lack of convergence in atomic coordinates in an NMR-based structure calculation also suggests atomic mobility. This paper describes a pattern in the coordinate uncertainties of backbone heavy atoms in NMR-derived structural “ensembles” first noted in the development of FindCore2 (previously called Expanded FindCore: DA Snyder, J Grullon, YJ Huang, R Tejero, GT Montelione, <i>Proteins: Structure, Function, and Bioinformatics </i>82 (S2), 219–230) and demonstrates that this pattern exists in coordinate variances across MD trajectories but not in crystallographic B-factors. This either suggests that MD trajectories and NMR “ensembles” capture motional behavior of peptide bond units not captured by B-factors or indicates a deficiency common to force fields used in both NMR and MD calculations.