Exotoxin A of the Pseudomonas(PEA) is a potently cytotoxic factor for immunotoxins(ITs) designing, via targeting tumor specific antigens as well as inhibition of the protein synthesis. Nonetheless, the molecular size of the factor is a challenge for the penetration of the factor to the solid tumor. So, PEA miniaturization based on the application of the capacity of the enzymatic active domain(domainIII) is an approach to overcome this problem. Bearing in mind, the structural stability as well as functional capacity of the domainIII was considered in this study compared to the PEA. In this regard, 3D structure of the PEA with the ID number:1IKQ was retrieved from PDB. Discovery Studio3.0 was used for the domainIII separation of the PEA. GROMACS5.07, containing gromos9643a1force field were used for simulation in 37°C (310°K), 100ps of the time for NVT and NPT steps and 2000ps for MD step. The results of this analysis revealed that the RMSD values of the domainIII are much less in the most steps compared to the PEA (specifically 5 steps with the RMSD difference ≈1Å). However, the RMSF showed equal values (except for 8 amino acids with the RMSD difference ≥1Å). Moreover, the alignments of the secondary structure of the domainIII represented 26 refolding including 10β-sheet→coil,2α-helix→ coil,3turn→ coil,7coil→β,3coil→α and 1coil→turn. Overall, the result of the study showed the structural stability of the domainIII without any changes in active site. So, it seems that the use of the domainIII may lead to maintaining its functionality in the composition of the immunotoxins.

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