Can Simulations and Modeling Decipher NMR Data for Conformational Equilibria? Arginine-Vasopressin

Hänsele E, Saleh N, Read CM, Banting L, Whitley DC, Clark T (2016)

Publication Status: Published

Publication Type: Journal article

Publication year: 2016

Journal

Journal of Chemical Information and Modeling American Chemical Society

Publisher: AMER CHEMICAL SOC

Book Volume: 56

Pages Range: 1798-1807

Journal Issue: 9

DOI: 10.1021/acs.jcim.6b00344

Abstract

Arginine vasopressin (AVP) has been suggested by molecular-dynamics (MD) simulations to exist as a mixture of conformations in solution. The H-1 and C-13 NMR chemical shifts of AVP in solution have been calculated for this conformational ensemble of ring conformations (identified from a 23 mu is 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 H-1 chemical shifts are most useful for assigning equilibrium concentrations of the conformations in this case. C-13 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 H-1 chemical shifts can be reproduced with a standard error of less than 0.24 ppm (<2.2 ppm for C-13). 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.

Authors with CRIS profile

Elke Hänsele Computer-Chemie-Centrum Noureldin Saleh Computer-Chemie-Centrum Timothy Clark Computer-Chemie-Centrum

Involved external institutions

University of Portsmouth GB United Kingdom (GB)

How to cite

APA:

Hänsele, E., Saleh, N., Read, C.M., Banting, L., Whitley, D.C., & Clark, T. (2016). Can Simulations and Modeling Decipher NMR Data for Conformational Equilibria? Arginine-Vasopressin. Journal of Chemical Information and Modeling, 56(9), 1798-1807. https://dx.doi.org/10.1021/acs.jcim.6b00344

MLA:

Hänsele, Elke, et al. "Can Simulations and Modeling Decipher NMR Data for Conformational Equilibria? Arginine-Vasopressin." Journal of Chemical Information and Modeling 56.9 (2016): 1798-1807.

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