We work on the characterization of hydrophobic gating in biological ion channels with the aim to extract general principles valid also for the design of artificial nanopores. We are currently working on two channels: CRAC and hERG. Given the knowledge of the open and closed state, we aim to compute the transition path of the opening mechanism. While hERG is expected to exhibit a classical gating mechanism triggered by a membrane potential change that displaces a charged helix of the Voltage Sensor Domain, experimental data suggest that CRAC might exhibit a hydrophobic gating mechanism due to a reorientation of a group of critical hydrophobic side chains lining the pore wall. In both cases our strategy entails the computation of a first guess of the transition path by means of Targeted Molecular Dynamics, followed by a calculation with the String method in collective variables to relax it to the minimum free energy path.