The protonated serine octamer (Ser 8 H + , C 24 H 57 N 8 O 24 + , see Figure ) is a relatively large molecular system comprising 113 atoms. Its structure was investigated using helium-tagging IR spectroscopy by comparing computed harmonic frequencies with experimental spectra. An application of the VPT2 method for this system is computationally not feasible. We have done a simple benchmark for computational timings (details are in ESI) and determined that in this case a VPT2 calculation is equivalent to a MD simulation with about 6 -12 × 10 3 frames. In addition, the VPT2 method is not reliable in application to vibrations with large amplitudes. On the other side, using molecular dynamics a decent representation of the Ser 8 H + molecular ensemble can be reached even with fewer than 6,000 frames.