The experimental CD spectra of L-AADKP indicate that the cyclic dipeptide can assume two conformations in solution. The conformer producing the positive n-p* CD band is lower in energy as indicated by the low-temperature CD spectra. The solvents TEP, methanol and water favor the formation of the conformer producing the negative n-p* CD band. In acetonitrile, the conformer producing the positive n-p* CD band is lower in energy as indicated by the resultant positive CD band.
Molecular mechanics results of AMBER and CHARMM indicate two conformers of L-AADKP in a vacuum, and to this extent agreement berween theoretical and experimental data is shown. Calculated CD spectra based on both AMBER and CHARMM vacuum conformations do not reproduce the negative/positive sign pattern of the experimental n-p* CD band in TEP or the positive n-p* CD band in acetonitrile.
Solvated molecular mechanics calculations of both AMBER and CHARMM indicate a single conformer. The CD spectra calculated from these results are in contrast to experimental observations. A conformer with a positive torsion angle b would produce a theoretical CD spectrum which would be in agreement with the experimental results where the n-p* transition is concerned. This is not predicted for both AMBER and CHARMM due to the increasing electrostatic energy as the torsion angle b assumes positive values.
MD simulations at 300 and 143 K provide an indication of the energy barrier for conformational interchange between the two predicted conformers. This value is consistent with the predicted barrier from molecular mechanics calculations.
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