Structural And Functional Optimization Of SS1P Based On In- Silico Simulation

Immunotoxin (IT) therapy is promising approach for targeted cancer therapy with the minimal sideeffects. These types of drugs are chimeric proteins with two main parts including death and liganddomains. Accordingly, structural and functional characterization of these types of drugs, based onin-silico simulation, could be providing suitable context for optimization as well as innovation incommon immunotoxins. Bearing in mind, structural optimization of SS1P immunotoxin wasconsidered in this study. In this regard, the protein sequence of the SS1P was retrieved fromcorresponding database such as Google patent. Structural characterization of the immunotoxin wasperformed via Intrproscan5 and Blast programs. On the other hand, the protein sequence of themesothelin as specific target of this drug was retrieved from NCBI databank. MODELLER9.15 wereused for structural modeling of the sequences. PROTEINATLAS database were used for assessmentthe expression of the antigen. Furthermore, HADDOCK were used for evaluation the bindingaffinity. Finally, all statistical analysis were expressed with SPSS 21.0 (SPSS Inc., Chicago, IL, USA).The results of the sequence characterization of the SS1P lead to obvious two main parts in thesequence context including dsfv and PE which are linked to each other with G2S1. Moreover, thestructure stability of the protein were confirmed after simulation under 300°K, 100ps of the time forNVT and NPT steps and 20000ps (20ns) for MD step. On the other hand, molecular docking of themesothelin to the modeled IT as well as optimized IT were confirmed after simulation. Takentogether, the results of the present study provide in-silico approaches for optimization as well asinnovation in the common sequence context of its for novelty in drugs design .