posted on 2024-03-05, 17:44authored byReagan
J. Meredith, Mi-Kyung Yoon, Ian Carmichael, Anthony S. Serianni
MA’AT analysis
(J. Chem. Inf. Model. 2022, 62, 3135–3141) has been
applied to model exocyclic hydroxymethyl group conformation in methyl
β-D-glucopyranoside (βGlcOMe), methyl β-D-galactopyranoside
(βGalOMe), and methyl β-D-mannopyranoside (βManOMe)
in an unbiased manner. Using up to eight NMR J-couplings
sensitive to rotation about the C5–C6 bond (torsion angle ω),
two-state models of ω were obtained that are qualitatively consistent
with the relative populations of the gg, gt, and tg rotamers reported previously. MA’AT analysis gave consistent unbiased gt ⇌ tg models of ω in βGalOMe,
with gt more populated than tg and
mean values of ω for each population similar to those obtained
from aqueous 1-μs MD simulation. Using different combinations
of J-couplings had little effect on the βGalOMe
model in terms of the mean values of ω and circular standard
deviations (CSDs). In contrast, MA’AT analysis
of ω in βGlcOMe and βManOMe produced more than one
two-state model independent of the ensemble of J-values
used in the analyses. These models were characterized by gg ⇌ gt conformer exchange as expected, but
the mean values of ω in both conformers varied significantly
in the different fits, especially for the gg rotamer.
Constrained (biased) MA’AT analyses in which
only staggered geometries about ω were allowed gave RMSDs slightly
larger than those obtained from the unbiased fits, precluding an assignment
of an unbiased model. It is unclear why MA’AT analysis gives consistent and predictable unbiased models of ω
in βGalOMe but not in βGlcOMe and βManOMe. One possibility
is that the distribution of ω in one or both of the gg and gt conformers in the latter does
not conform to a von Mises function (i.e., is not Gaussian-like),
but rather to a broad and/or flat distribution that cannot be fit
by the current version of MA’AT. Nevertheless,
the results of this study provide new evidence of the ability of MA’AT analysis to treat multi-state conformational
exchange using only experimental NMR data, extending recent MA’AT applications to furanosyl ring pseudorotation
(Biochemistry2022, 61, 239–251).