Classical and quantum mechanical/molecular mechanical molecular dynamics simulations of alanine dipeptide in water: Comparisons with IR and vibrational circular dichroism spectra

We have implemented the combined quantum mechanical (QM)/molecular mechanical (MM) molecular dynamics (MD) simulations of alanine dipeptide in water along with the polarizable and nonpolarizable classical MD simulations with different models of water. For the QM/MM MD simulation, the alanine dipeptide is treated with the AM1 or PM3 approximations and the fluctuating solute dipole moment is calculated by the Mulliken population analysis. For the classical MD simulations, the solute is treated with the polarizable or nonpolarizable AMBER and polarizable CHARMM force fields and water is treated with the TIP3P, TIP4P, or TIP5P model. It is found that the relative populations of right-handed α -helix and extended Β and PII conformations in the simulation trajectory strongly depend on the simulation method. For the QM/MM MD simulations, the PM3/MM shows that the PII conformation is dominant, whereas the AM1/MM predicts that the dominant conformation is αR. Polarizable CHARMM force field gives almost exclusively PII conformation and other force fields predict that both α -helical and extended (Β and PII) conformations are populated with varying extents. Solvation environment around the dipeptide is investigated by examining the radial distribution functions and numbers and lifetimes of hydrogen bonds. Comparing the simulated IR and vibrational circular dichroism spectra with experimental results, we concluded that the dipeptide adopts the PII conformation and PM3/MM, AMBER03 with TIP4P water, and AMBER polarizable force fields are acceptable for structure determination of the dipeptide considered in this paper.