Modeling infrared and vibrational circular dichroism spectra of complex systems: the DFTB/fluctuating charges route

Abstract

Simulating vibrational spectra of large biomolecular systems in aqueous environments remains a challenge in computational chemistry due to the complex interactions between solutes and solvents. In this study, we employ the density functional tight-binding (DFTB) method, coupled with the fluctuating charges (FQ) force field, to simulate infrared (IR) and vibrational circular dichroism (VCD) spectra of solvated large biomolecules. We focus on three representative systems: the doxorubicin/DNA intercalation complex, ubiquitin, and hen egg white lysozyme. By using molecular dynamics (MD) trajectories to sample the conformational space, we compute spectra for multiple snapshots, employing different DFTB Hamiltonians, including SCC-DFTB, DFTB3, and GFN1-xTB. Our results demonstrate the accuracy and computational efficiency of the DFTB/FQ method in reproducing experimental spectral features, particularly for large, solvated systems which cannot be afforded by other ab initio methodologies. The results of this work highlight the potential of DFTB/FQ as a scalable method for simulating vibrational properties in complex molecular systems.