Journal of Physical Chemistry B 2007-12-20

Conformational analysis of L-prolines in water.

Abil E Aliev, Denis Courtier-Murias

Index: J. Phys. Chem. B 111 , 14034-14042, (2007)

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Abstract

The results of the ring conformational analysis of L-proline, N-acetyl-L-proline, and trans-4-hydroxy-L-proline by NMR combined with calculations using density functional theory (DFT) and molecular dynamics (MD) are reported. Accurate values of 1H-1H J-couplings in water and other solvents have been determined. Using a two-site equilibrium model, the Cgamma-endo conformer of L-proline in water has been identified as intermediate between gammaTdelta [twist(Cgamma-endo, Cdelta-exo)] and gammaE [envelope(Cgamma-endo)] and the Cgamma-exo conformer as betaTgamma. Both conformers were equally populated at room temperature. The N-acetyl [cis-rotamer gammaTbeta(80%)/gammaE(20%) and trans-rotamer gammaTbeta(61%)/gammaE(39%)] and 4-hydroxy (gammaEpsilon) derivatives showed significant changes in both the population and the geometries of the preferred ring conformers. The combination of NMR predicted populations with the DFT B3LYP/6-311+G(2d,p)/IEFPCM calculations proved successful, resulting in fairly accurate predictions of J-couplings. Simulations using MD were mostly in favor of the two-site equilibrium model between Cgamma-endo and Cgamma-exo conformers, similar to that used for the analysis of NMR J-couplings. Various force fields examined for MD simulations failed to reproduce the ring conformational geometries and populations of L-proline in water accurately, while significantly better agreement with NMR was found for trans-N-acetyl-L-proline using GROMOS and AMBER force fields.