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

TL;DR

This study compares different force fields, including multipolar and point charge models, in simulating the conformational dynamics and amide-I spectroscopy of trialanine, showing that multipolar models better match experimental results.

Contribution

It introduces multipolar force fields for amide-I spectroscopy and demonstrates their improved accuracy over traditional point charge models in simulating peptide dynamics.

Findings

Multipolar force fields yield spectra closer to experimental data.

MTP simulations show conformational populations consistent with Bayesian analysis.

Full normal mode analysis with MTP accurately describes peptide dynamics.

Abstract

The dynamics and spectroscopy of N-methyl-acetamide (NMA) and trialanine in solution is characterized from molecular dynamics (MD) 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 1-d 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 SCC-DFTB simulations, compared with 25 cm$^{-1}$ from experiment. The frequency trajectory required for determining the frequency fluctuation correlation function (FFCF) is determined from individual (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 $\Delta_0^2$ from simulations using MTP and analysis based on FNM are all consistent with experiments for (Ala)$_3$. Contrary to that, 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 $\Delta_0^2$ 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 , whereas that covered by the MTP-based simulations is dominated by P$_{\rm II}$ which agrees with and confirms recently reported, Bayesian-refined populations based on 1-dimensional infrared experiments. Full normal mode analysis together with a MTP representation provides a meaningful model to correctly describe the dynamics of hydrated trialanine.