SMAH - Molecular Horizons PhD Exit Seminar with Sandeep Inakollu

Vibrational spectroscopy is an invaluable tool to study the structural configurations and electrostatic interactions in (bio)molecular systems. However, interpretation of the structural information from the experimental spectra is not always straightforward and often rely on computational methods. One of the most established, computationally economical, and harmonic approximation based approach is normal mode analysis (NMA); however, it is not suitable for floppy molecules. Molecular dynamics (MD) simulation-based methods can be used to compute the vibrational spectra “on the fly”, but they become computationally expensive, especially with ab initio and DFT methods. In this project, we optimised the Fourier transform of the dipole autocorrelation function (FT-DAC) method with the approximated DFT based method, i.e. third-order density-functional tight-binding theory (DFTB3).

We systemically benchmarked the vibrational frequency calculations using DFTB3 model with NMA and FT-DAC methods. The results were compared against the experimental and B3LYP/cc-pVTZ data. We have also demonstrated the significance of anharmonicity and conformational sampling in vibrational spectral calculations in flexible molecules. Then, we studied the nuclear quantum effect (NQE) on the FT-DAC spectra of serine using thermostat ring-polymer MD simulations. At lower temperature, there is some influence of NQE on the dynamics of hydroxyl and amine hydrogens.

Finally, the benchmarked DFTB3/FT-DAC method is extended to condensed phase systems using the quantum mechanical/molecular mechanical (QM/MM) approach. Our method predicted the vibrational frequencies accurately in the non hydrogen-bonding environment. Treatment of polarisation at the QM/MM boundary using the Drude polarisable force field improved the results in hydrogen-bonding environment. Additionally, a linear correlation is also established between the solvent-induced electric field and the vibrational frequency shift, also known as vibrational Stark effect.