Multipolar Force Fields for Amide-I Spectroscopy from Conformational Dynamics of the Alanine Trimer

The dynamics and spectroscopy of N-methyl-acetamide (NMA) and trialanine in solution are characterized from molecular dynamics simulations using different energy functions, including a conventional point charge (PC)-based force field, one based on a multipolar (MTP) representation of the electrostatics, and a semiempirical DFT method. For the 1D infrared spectra, the frequency splitting between the two amide-I groups is 10 cm^–1 from the PC, 13 cm^–1 from the MTP, and 47 cm^–1 from self-consistent charge density functional tight-binding (SCC-DFTB) simulations, compared with 25 cm^–1 from experiment. The frequency trajectory required for the frequency fluctuation correlation function (FFCF) is determined from individual normal mode (INM) and full normal mode (FNM) analyses of the amide-I vibrations. The spectroscopy, time-zero magnitude of the FFCF C(t = 0), and the static component Δ₀² from simulations using MTP and analysis based on FNM are all consistent with experiments for (Ala)₃. Contrary to this, for the analysis excluding mode–mode coupling (INM), the FFCF decays to zero too rapidly and for simulations with a PC-based force field, the Δ₀² is too small by a factor of two compared with experiments. Simulations with SCC-DFTB agree better with experiment for these observables than those from PC-based simulations. The conformational ensemble sampled from simulations using PCs is consistent with the literature (including P_II, β, α_R, and α_L), whereas that covered by the MTP-based simulations is dominated by P_II with some contributions from β and α_R. This agrees with and confirms recently reported Bayesian-refined populations based on 1D infrared experiments. FNM analysis together with a MTP representation provides a meaningful model to correctly describe the dynamics of hydrated trialanine.