Comparative Analysis of Commercial CCL21 and CCL21/IL1β Recombinant Proteins by in silico Tools

Abstract

One of the newest diagnostic methods and treatment of cancer is to design new drugs. It is now possible to design a drug with desired properties in theory and evaluate its therapeutic effects through bioinformatics tools. Among the studied drugs, those based on cytokine genes, which increase the body's immunity against cancer, are of great interest. Cytokines are small proteins that play an essential role in cell signaling and can affect the function and behavior of surrounding cells. CCL21 chemokine is one of the cytokines that possess antitumor properties has the potential for chemoattraction of T lymphocytes and dendritic cells. Interleukin 1 beta (IL1β) is a cytokine involving different cellular activities such as the activation of neutrophils, B-Cells, and T-Cells. In the present study, we designed a drug-based cytokine gene to activate T cells and B cells by inserting defined CCL21 epitope and IL1β peptide sequences into a protein construct. Molecular dynamics simulation was performed in Linux space using Gromex software. Results of RMSD, RMSF, and the radius of gyration obtained from the simulation showed the stability of both proteins, which indicated that there are no significant conformational differences between the commercial CCL21 and recombinant form. The interaction of synthetic construct and human CCL21 with the CCR7 receptor was also investigated by HADDOCK software. Obtained results showed no differences between these proteins, and recombinant protein has the same structural and conformational characteristics as human commercial CCL21.

Keywords

• cytokine
• chemokine
• ccl21
• docking
• molecular dynamics simulation