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Side Chain Conformational Distributions of a Small Protein Derived from Model-Free Analysis of a Large Set of Residual Dipolar Couplings

Published

Author(s)

Fang Li, Alexander Grishaev, Jinfa Ying, Adriaan Bax

Abstract

Accurate quantitative measurement of structural dispersion in proteins remains a prime challenge to both X-ray crystallography and NMR spectroscopy. An approach based on measurement of many residual dipolar couplings (RDCs) in differentially orienting aqueous liquid crystalline solutions is used to obtain modelfree definition of the sidechain Chi1 distribution sampled by each residue in solution. Applied to the small model protein GB3, the RDC data are compatible with a single narrow distribution of sidechain chi1 angles for only about 40% of the residues. For more than half of the residues, populations greater than 10% for a second rotamer are observed, and four residues require sampling of three rotameric states to fit the RDC data. In virtually all cases, sampled Chi1 values are found to center closely around ideal g-, g+ and t rotameric angles, even though no such restraint is used when deriving the sampled angles. The root-mean-square difference between experimental 3JHαHβ couplings and those predicted by the Haasnoot-parameterized, motion-adjusted Karplus equation reduces from 2.05 Hz to 0.75 Hz when using the new rotamer analysis instead of the 1.1-Angstrom X-ray structure as input for the dihedral angles. A comparison between observed and predicted 3JHαHβ values suggests that the root-mean-square amplitude of Chi1 angle fluctuations within a given rotamer well is approximately 20 degrees.
Citation
Journal of the American Chemical Society

Keywords

Ensemble representation, Liquid crystal, Karplus equation, Protein dynamics, Rotamer distribution, Sidechain dynamics

Citation

Li, F. , Grishaev, A. , Ying, J. and Bax, A. (2015), Side Chain Conformational Distributions of a Small Protein Derived from Model-Free Analysis of a Large Set of Residual Dipolar Couplings, Journal of the American Chemical Society, [online], https://doi.org/10.1021/jacs.5b10072, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=919345 (Accessed April 15, 2024)
Created November 1, 2015, Updated October 13, 2022