Fig. 3.

Molecular modeling of phenotype-characterized cancer-associated EpCAM mutations. A Significant local conformational changes observed in wild type EpCAM and its mutants, L240A and C66Y. Conformational changes in the EpCAM protein and its mutants were analyzed during molecular dynamics simulations. The original EpCAM structure (PDB ID: 4MZV) is shown in yellow with the TY-loop highlighted in green, while the average predicted structure is depicted in blue with the TY-1 loop highlighted in magenta. B Graphical representation of backbone conformations, C Radius of gyration, D Residual fluctuations, and E Solvent-accessible surface area (SASA). F Probability distribution function plots for EpCAM-WT, EpCAM-L240A and EpCAM-C66Y. G Analysis of intra-protein hydrogen bonds for EpCAM-WT (black), EpCAM-L240A ​ (cyan), and EpCAM-C66Y​(orange). H Conformational changes in EpCAM Protein structures during MD simulation. Superimposed figures of EpCAM_WT with EpCAM_L240A and EpCAM_WT with EpCAM_C66Y. I Principal components Analysis of EpCAM_WT, EpCAM mutants L240A and C66Y. J Dynamic cross correlation matrix (DCCM) of backbone atoms of EpCAM-WT, EpCAM-L240A and EpCAM-C66Y. DCCM maps, obtained from 1 μs trajectories, contain contours of different colours. Correlated motion and anti-correlated motions are represented by amber and blue colours, respectively. The Black coloured box indicated the correlation between the TY-loop and RCD regions