HyGate consisted of four main research lines: hydrophobic gating of model nanopores, gating mechanisms of biological ion channels (including hERG, CRAC, Kv 1.2 BK), coarse-grained models of drying/wetting in nanopores, and design of biomimetic nanopores and circuits. The adopted approaches combined molecular dynamics with accelerated sampling techniques for rare events, with a network representation of the ion channel, or with “first principles” coarse-grained models. The first research line showed how hydrophobic gating could be accelerated by the presence of hydrophobic gases, which enhance low-density fluctuations of water in hydrophobic confinement; further studies highlighted the peculiar wetting behaviour of subnanometer pores. Biological simulations revealed how motion propagates from the “sensor” of an ion channel to its gate via contacts between amino acids (the gating pathways) to achieve control of ionic currents. We studied an important cardiac channel, hERG, its pathological and artificial mutations, and its interactions with a drug; the same approach was used to investigate hydrophobic gating in the calcium channel CRAC and other gating mechanisms. Thirdly, microscopically informed coarse-grained models were developed to study the behaviour of nanopores on experimentally relevant timescales when hydrophobic gating is present and extrinsic parameters, such as voltage or pressure, are changed. Finally, information from all research lines converged in the biomimetic design of nanopores exploiting hydrophobic gating to realise fluidic memristive nanopores and materials endowed with negative compressibility.
The results of HyGate have been published in more than 30 peer-reviewed publications; two international workshops “Frontiers in Ion Channels and Nanopores (FICN)” were organised and an ERC proof-of-concept project explored the impact of HyGate results on high performance liquid chromatography.
