Fig. 17: Overview of the computational pipeline.

a Mutant structures are generated using AlphaFold 3 and the impact of point mutations on protein stability is predicted using ΔΔG predictors. b The structural effects of these mutations are analysed alongside existing ligands. This involves quantifying structural changes with TM-Align, investigating residue centrality and functional communities with PCN-Miner, visualizing embeddings and predicting pathogenicity with ESM2, and investigating the structural stabilization/destabilization effects of both mutations and ligands using molecular dynamics simulations. c Molecular docking was performed on the TTR binding sites of the mutant structures using DiffDock and AutoDock Vina, evaluating binding affinities and identifying optimal ligands for each mutation. d DiffSBDD was used to generate new ligands or optimize existing ones to effectively bind specific mutations.