To aid exploration of the likely impact of mutations on protein function, the mutation profile for a target can be interrogated using the interactive mutation tool (Figure 1C). This tool displays the mutation frequency along the protein sequence, aligned with interactive and scalable tracks for evidence of each amino acid in the following areas: position in functional domains; residues known to be post-translationally modified; residues involved in ligand or drug binding; hotspots in protein-protein interfaces; residues participating in ligandable cavities (as assessed by the canSAR 3D ligandability pipeline) belonging to the protein of interest or formed as a result of a direct interaction with a protein partner. The interactive tool additionally selects representative 3D structures to allow the user to display the position of the mutation on the appropriate 3D structure of the target of interest. This tool can help generate hypotheses about the role of a particular mutation in ligand-binding, interference with drug binding, or regulatory activity. Users can navigate between different cohorts and studies, fine tuning their hypothesis generation.
