Direct calculations of vibrational absorption and circular dichroism spectra of alanine dipeptide analog in water: Quantum mechanical/molecular mechanical molecular dynamics simulations

The vibrational absorption (IR) and vibrational circular dichroism (VCD) spectra of alanine dipeptide analog in water are directly calculated by Fourier transforming the time correlation functions of the electric and magnetic dipole moments, which are calculated using the dynamic partial charges and trajectory of the peptide generated from the quantum mechanical/molecular mechanical molecular dynamics simulations. The alanine dipeptide analog is treated at the Hartree-Fock level with 3-21G, 4-31G, 6-31G, and 6-31 G basis sets and the solvent H₂ O is modeled with the TIP3P water. The atomic partial charges are obtained from the Löwdin population analysis, which gives consistent IR spectral profiles irrespective of the basis sets used. The simulated VCD spectrum by a polyproline II (PII) -dominant trajectory is compatible with the previous experimental results of the polyproline peptides, where the amide I and II VCD bands are negative couplets with a weak positive peak to the high frequency region. The sampling efficiency of the PII conformer is much lower than the other ones at all basis levels used. The simulated VCD spectrum of α -helix averaged over five trajectories has the reverse sign pattern compared to the PII spectrum and is found to be consistent with the previously observed spectral features of α -helical polypeptides. The sign patterns of the Β -strand VCD spectrum are qualitatively similar to the experimental spectra of Β -sheet rich proteins. The VCD spectra obtained from the trajectories containing several extended conformers such as Β and PII are not clearly distinguishable from the Β -strand-dominant spectra. It is interesting that the PII and the coil VCD spectra coincide in sign pattern and relative intensity for all amide modes. This demonstrates that the negative couplet structures of the amide I and II VCD spectra do not necessarily prove the dominance of either P_II or coil conformation. We anticipate that the present method can be used to directly simulate the IR and VCD spectra of structurally heterogeneous biomolecules in condensed phases.