Fig. 3: Integrated computational framework for the structural and functional characterization of transthyretin (TTR) variants.

A multi-level computational analysis has been performed by combining structural prediction, sequence-based representation, and dynamic simulations of TTR variants. A Structural alignment between the structures of variants. B Experimental Validation of the predicted structures. C Two-dimensional UMAP projection of TTR variants for classifying pathogenic and bening variants. D Distribution of TM-Scores for the Variants reveals that structure of the monomer are more conserved. E Receiver operating characteristic (ROC) curves illustrating the classification performance in distinguishing benign and pathogenic TTR variants. F PCN analysis identified changes at mesoscale in variants. F Docking pose of Acoramidis on a generatively designed Y98F variant, revealing predicted binding interactions from AI-based docking. G RMSD time evolution from molecular dynamics simulations of the V50M variant, supporting the structural stability of the predicted model. H Selected Ligands have been optimised. I Molecular Dynamics Simulation of the binding.