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作者 Weise, Christoph Felix
書名 Structure and orientation of the alanine dipeptide and small amides in a water-based liquid crystal
國際標準書號 0496374211
book jacket
說明 259 p
附註 Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 2208
Supervisor: James C. Weisshaar
Thesis (Ph.D.)--The University of Wisconsin - Madison, 2003
The capped alanine dipeptide (AcAlaNHMe) is a molecular benchmark employed in the development of tools for protein structure prediction. It contains flexible dihedral angles &phis; and psi and thus represents a simple model of the peptide backbone. Previous experiments have failed to unambiguously determine the distribution of conformations {&phis;, psi} in water. Competing force-fields make conflicting predictions regarding the relative importance of the two solution conformers lowest in energy, a polyproline turn P II with approximate dihedrals {-90°, 130°} and a right-handed alpha-helix alphaR near {-60°, -60°}. We extracted dipolar couplings of the dipeptide via LX-NMR, employing an orienting medium of magnetically aligned cesium perfluorooctanoate (CsPFO) bicelles in water. Experiments with isotopically unlabelled AcAlaNHMe and a 13C-labelled variant provided 9 and 13 couplings, respectively. Least-squares fits with one or two rigid trial geometries derived from electronic structure calculations succeed when {&phis;, psi} adopts a PII conformation, but fail for the alphaR conformer. Incorporating corrections for hindered methyl rotations, small amplitude dihedral torsions and other internal motions within conformational wells did not alter conclusions drawn from a simple rigid model
We examined the possibility that an alphaR conformer eluded detection due to a fortuitously small orientation tensor, rather than a small relative population, by investigating the orientation of N-methylated formamides and acetamides in CsPFO/water via LX-NMR. Large orientation strengths are observed for amides that can simultaneously immerse the carbonyl group into the aqueous phase and insert N-methyl groups into the hydrophobic bicelle interior. This mechanism is consistent with the structure of the S matrices. All amides display substantial couplings irrespective of structure, offering no evidence that an alphaR structure exists in a negligibly oriented state. Neither are there indications that AcAlaNHMe is driven into a particular conformation by the orienting interaction, since the dipeptide is weakly oriented in the liquid crystal
Finally, we modified procedures for deriving high-accuracy structural and orientational parameters from dipolar couplings, focusing on vibrational corrections for formamide. Vibrations are significantly attenuated by the solvent, suggesting that simple analytical models may fail by overestimating the corrections. Improvements in vibrational models therefore promise to increase the accuracy of derived parameters
School code: 0262
Host Item Dissertation Abstracts International 64-05B
主題 Chemistry, Physical
Biophysics, General
Alt Author The University of Wisconsin - Madison
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