Structural modeling and functionality assessment of IMTOX immunotoxin family in quasi-physiological circumstance

Commensurate with the spread of technology various therapies in the field of cancer such as immunotoxin has been developed. Hence, recognizing the features of these drugs could be provide opportunity for development, which are considered in this study in association with IMTOX family.Material and methods:In this study, sequences of IMTOX were achieved based on patents. NCBI and PDB databanks were used to achievement the protein sequences and 3D structures. Modeller were employed to modeling and assembling via homology modeling method. ERRAT, Verify 3D and RAMPAGE programs were used to determine the quality of the models. Evaluation the thermostability in quasi-physiological condition were carried out by GROMACS. Functionality features were assayed by affinity to corresponding antigens and immunogenicity properties which evaluated by HADDOCK and IEDB programs, respectively. Result:Literature review has led to obvious 3 isoforms of IMTOX family, including IMTOX19, IMTOX22 and IMTOX25 with the ability to target CD19, CD22 and CD25 for lymphoma treatment, respectively. Chain A of the Ricin and various antibodies fragments were discovery in the sequence context of these drugs. Structural modeling of the components of drugs and corresponding antigens showed suitable quality. Fragments assembling resulted in the production of several isoforms from each drug, which one of them showed the suitable quality at 37°C. Meanwhile, appropriate affinity to corresponding antigens and immunogenicity feature of these drugs were obvious. Discussion and conclusion:Generally, the results of this study has led to introduced functionally models of IMTOX family which can used in lab and opportunity for drug optimization.

کلیدواژه ها:

Cancer ، immunotoxin ، IMTOX ، Modeling ، Simulation