There have been several sophisticated studies of the effect of replacement of H by D on the 13C NMR spectra of proteins.1,2 The largest effects are on the substituted atom with smaller isotope shifts observed for increasingly distant atoms. The interpretation of the observed effects is so far strictly empirical based on assumptions that are difficult to test experimentally . The isotope effect on chemical shift is the difference in the zero point and thermal average of the chemical shift variation with very small excursions in molecular geometry. We have developed3 and are expanding a method for the computation of this effect based on a local mode treatment. In this approach we compute the change in all the chemical shifts of the molecule as a function of Cα –H bond length and bond angles and then average this variation over the probability distributions of these excursions for H and D. In the present study we apply this computational method to the case of a “dipeptide” N-acetyl-glycine-amide with CαD substitution as a function of φ and ψ. We the then repeat this φ, ψ variation examining the effect of substitution at Cα with a R = -CH3,-CH2OH and -CH(CH3)2. The current empirical approach assumes that the φ, ψ variation is independent of the R group. 1. Maltsev, A. S.; Ying, J.; Bax, A., Deuterium isotope shifts for backbone 1H, 15N and 13C nuclei in intrinsically disordered protein α synuclein, J. Biomol. NMR (2012), 54(2), 181. 2. Zhang, D.; Tugarinov, V., Accurate measurements of the effects of deuteration at backbone amide positions on the chemical shifts of 15N, 13Cα, 13Cβ, 13CO and 1Hα nuclei in proteins, J. Biomol. NMR (2013), 56(2), 169.2. 3. Yang, K. S.; Hudson, B. S. Computation of Deuterium Isotope Perturbation of 13C NMR Chemical Shifts of Alkanes: A Local Mode Zero-Point Level Approach, J. Phys. Chem. A 2010, 114, 12283.

What can we learn from 13C NMR studies of CαD substituted dipeptides: A computational study

251st National Meeting (2016)

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