Advanced computational modelling approaches are employed to generate and validate Slo3 homology models for virtual screening and compound optimisation. First, refined Slo3 models will be developed using state-of-the-art methods. In silico predictions of binding sites will be combined with experimental data to validate and evaluate potential binding sites. To understand the dynamics and effects of drug–ion channel interactions, a combination of targeted mutagenesis of putative binding sites, electrophysiology, molecular pharmacology, and mathematical and three-dimensional computational modelling will be applied.