Measurability of side chain rotational isomer populations: NMR and molecular mechanics of cobalt glycyl-leucine dipeptide model system

Physics – Biological Physics

Scientific paper

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21 pages, 4 figures (1 new), 4 tables (2 new), LaTeX2e and REVTeX v4, supporting material, updated author affiliations, v2 als

Scientific paper

The cobalt glycyl-leucine dipeptide is a model system for studying the effects of Karplus equation calibration, molecular mechanics accuracy, backbone conformation, and thermal motions on the measurability of side chain rotational isomer populations. We analyze measurements of 8 vicinal coupling constants about the alpha to beta-carbon and beta to gamma-carbon bonds of the leucine side chain and of 10 NOESY cross relaxation rates across these bonds. Molecular mechanics and peptide and protein crystallographic databases are an essential part of this analysis because they independently suggest that the trans gauche-plus and gauche-minus trans rotational isomers of the leucine side chain predominate. They also both suggest that puckering of the cobalt dipeptide ring system reduces the gauche-plus gauche-plus rotational isomer population to less than about 10%. At the present +/- 1 Hz calibration accuracy of Karplus equations for vicinal coupling constants, the predominant trans gauche-plus and gauche-minus trans rotational isomer populations can be measured with about 5% accuracy, but the population of the gauche-plus gauche-plus rotational isomer is probably very near or just below the limit of measurability. These estimates also depend upon qualitative assessments of the accuracy of the molecular mechanics energy wells. We introduce gel graphics that are ideally suited to presenting qualitative error and measurability estimates.

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