Simulation And Stability Assessment Of Anti-EpCAM Immunotoxin For Multiple Cancer Therapy

Epithelial cell adhesion molecule (EpCAM) is a dominant antigen in human colon carcinoma tissue.Topology features of this antigen is different in normal and malignancies condition, so that innormal cells is predominantly located in intercellular spaces and is sequestered on normalepithelia and, therefore, much less accessible to antibodies than EpCAM in cancer tissue.Accordingly, EpCAM was considered as a suitable candidate for cancer target therapy viaimmunotoxins (ITs) development. In this regard, several ITs have been developed which could beprovided context for ITs optimization. Bearing in mind, we have focused on the stability assessmentof an anti-EpCAM-IT (anti-Ep-IT) for designing a novel IT. In this regard, 3D structure of EpCAM andtoxin segments of anti-Ep-IT were retrieved from PDB, with the ID numbers 4MZV, 1IKQ,respectively. Discovery Studio3.0 was used for separation of the ligands and water molecules.Alignment of the antibody (Ab) fragment of anti-Ep-IT was performed through BLAST-p, and SWISSMODELdatabase was used for Ab modeling. Moreover, IT modeling was accomplished throughMODELLE-9.15. G-OMACS5.07, containing gromos96 43a1 force field were used for simulation300°K, 100ps of the time for NVT and NPT steps and 20000ps(20ns) for MD step. -MSD and -MSFplots were drown by Excel. Finally, E-AAT database was used for quality assessment of thestructure. In general, the both modeling results and quality evaluations of them were satisfactoryfor designing IT. Moreover, -MSD and -MSF plots reveal that IT stability has preserved during thesimulation. On the whole, our findings led to designing a new anti-Ep-IT with more stability.