Fast and accurate hybrid QM//MM approach for computing anharmonic corrections to vibrational frequencies

We have developed and tested a new time-effective and accurate hybrid QM//MM generalized second-order vibrational perturbation theory (GVPT2) approach. In this approach, two different levels of theory were used, a high level one (DFT) for computing the harmonic spectrum and a lower fast one (Molecular Mechanic) for the anharmonic corrections. To validate our approach, we used B2PLYP/def2-TZVPP as the high-level method, and the MMFF94 method for the anharmonic corrections as the low-level method. The calculations were carried out on 28 molecules (containing from 2 to 47 atoms) covering a broad range of vibrational modes present in organic molecules. We find that this fast hybrid method reproduces the experimental frequencies with a very good accuracy for organic and bio-molecules. The root-mean-square deviation (RMSD) is about 27 cm -1 while the full B3LYP/SNSD simulation reproduces the experimental values with a RMSD of about 41 cm -1. Concerning the computational time, the hybrid B2PLYP//MMFF94 approach considerably outperforms the full B3LYP/SNSD: for the larger molecule of our set (a dipeptide containing 47 atoms), the anharmonic corrections are 2300 times faster using hybrid MMFF94 rather than full B3LYP, which represents an additional computation time to the harmonic calculation of merely 9 %, instead of 32100 % with the full B3LYP approach. This time-effective and accurate alternative to the traditional GVPT2 approach will allow the spectroscopy community to explore anharmonic effects in larger biomolecules, which are generally unaffordable.