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Can Simulations and Modeling Decipher NMR Data for Conformational Equilibria? Arginine–Vasopressin
journal contribution
posted on 2016-09-01, 00:00 authored by Elke Haensele, Noureldin Saleh, Christopher M. Read, Lee Banting, David
C. Whitley, Timothy ClarkArginine
vasopressin (AVP) has been suggested by molecular-dynamics
(MD) simulations to exist as a mixture of conformations in solution.
The 1H and 13C NMR chemical shifts of AVP in
solution have been calculated for this conformational ensemble of
ring conformations (identified from a 23 μs molecular-dynamics
simulation). The relative free energies of these conformations were
calculated using classical metadynamics simulations in explicit water.
Chemical shifts for representative conformations were calculated using
density-functional theory. Comparison with experiment and analysis
of the results suggests that the 1H chemical shifts are
most useful for assigning equilibrium concentrations of the conformations
in this case. 13C chemical shifts distinguish less clearly
between conformations, and the distances calculated from the nuclear
Overhauser effect do not allow the conformations to be assigned clearly.
The 1H chemical shifts can be reproduced with a standard
error of less than 0.24 ppm (<2.2 ppm for 13C). The
combined experimental and theoretical results suggest that AVP exists
in an equilibrium of approximately 70% saddlelike and 30% clinched open conformations. Both newly
introduced statistical metrics designed to judge the significance
of the results and Smith and Goodman’s DP4 probabilities are
presented.
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13 C chemical shifts13 C NMR chemical shiftsConformational Equilibriarepresentative conformationsequilibrium concentrationsmetadynamics simulationsModeling Decipher NMR Datamolecular-dynamics simulation13 Cdensity-functional theoryDPring conformations1 H chemical shifts1 H23 μMDAVPchemical shiftsOverhauser effect
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