The effect of motional averaging on the calculation of NMR-derived structural properties

• Published in: Proteins, structure, function, and bioinformatics structure, function, and bioinformatics, 1999-09, Vol.36 (4), p.542-555
• Main Authors: Daura, Xavier, Antes, Iris, van Gunsteren, Wilfred F., Thiel, Walter, Mark, Alan E.
• Format: Article
• Language: English
• Subjects: 3J-coupling constant; chemical shift; Computer Simulation; Kinetics; Methanol; Models, Molecular; molecular dynamics; NMR; NOE distance; Nuclear Magnetic Resonance, Biomolecular - methods; peptides; Peptides - chemistry; Peptides - metabolism; Protein Conformation; Protein Folding; Proteins - chemistry; Proteins - metabolism; Protons; Sample Size; Sensitivity and Specificity; Temperature; Thermodynamics
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/(SICI)1097-0134(19990901)36:4<542::AID-PROT17>3.0.CO;2-M

The effect of motional averaging when relating structural properties inferred from nuclear magnetic resonance (NMR) experiments to molecular dynamics simulations of peptides is considered. In particular, the effect of changing populations of conformations, the extent of sampling, and the sampling frequency on the estimation of nuclear Overhauser effect (NOE) inter‐proton distances, vicinal 3J‐coupling constants, and chemical shifts are investigated. The analysis is based on 50‐ns simulations of a β‐heptapeptide in methanol at 298 K, 340 K, 350 K, and 360 K. This peptide undergoes reversible folding and samples a significant proportion of the available conformational space during the simulations, with at 298 K being predominantly folded and at 360 K being predominantly unfolded. The work highlights the fact that when motional averaging is included, NMR data has only limited capacity to distinguish between a single fully folded peptide conformation and various mixtures of folded and unfolded conformations. Proteins 1999;36:556–564. © 1999 Wiley‐Liss, Inc.