Fig. 4.

Bioinformatics and MD simulation-based analysis of EpCAM mutations. A Computational tools, including SIFT (Sorting Intolerant From Tolerant), PolyPhen (Polymorphism Phenotyping), and Mutation Assessor, were used to evaluate structural alterations for each mutation. Scores ranged from 0 (least damaging) to 1 (most damaging). The combined scoring provides a comprehensive view of the most damaging mutations, as shown in the figure. Molecular dynamics (MD) simulations were performed for seven lung cancer-associated mutations to characterize various structural and dynamic parameters. B Principal Component Analysis (PCA) showing 2D projection correlation maps from MD simulations for the wild type (WT) EpCAM and its mutant structures. C Probability distribution functions of WT EpCAM (black) and mutants: D92V ( turquoise), E137A (orange), Y186C (blue), Q204E (brown), P84S ( gray), and Y215S ( (violet). D Root Mean Square (RMS) fluctuation spectrum of the TY loop replace and remove inset. E–F Structural changes observed during MD simulations by superimposing the WT EpCAM and mutant structures, specifically comparing WT EpCAM (black) and the N111K mutant. G Wild type EpCAM (black in colour) and N111K (brown in colour) RMSD, RMSF,RMS, Rg, SASA and H Hydrogen bonds