<p>Investigating proton tunneling in biological molecules at low temperatures presents a computational challenge that has garnered significant interest among theoretical chemists. This study becomes even more compelling when proton tunneling is mediated by resonance-assisted hydrogen bonds. Inspired by recent developments, an approach to explore the tunneling mechanism, using Fujikurin A–D molecules as model systems is proposed. The method is based on analyzing the differences in geometrical, electronic, and vibrational properties of equilibrium tautomers. Specifically, it is demonstrated that for Fujikurin A and D molecules is reasonable to assume that no proton transfer occurs, with the proton being completely delocalized between the donor and acceptor oxygens. An alternative yet equally plausible mechanism suggests that proton tunneling is completely decoupled from other molecular degrees of freedom, where the quantum state is described by a weighted superposition of the states of the isolated tautomers. In contrast, for the Fujikurin B molecule, however, proton tunneling governs the tautomeric equilibrium and occurs along a periodic path formed by distinct forward and back trajectories.</p> Graphical abstract <p></p>