In Silico Study Of The Increase In Potency About Cytokine Interleukin-21

Interleukin-21is a member of type I cytokine family which is reported in recent years, and has various biological functions, especially the most remarkable characteristic is that it can significantly regulates the immune activity of B cells and CD4+T cells. So we study how to improve the bioactivity of IL-21in order to make it antitumor or anti-infection drugs used in clinical treatment. With the development of computer, computer molecular simulation technology is widely used in many fields such as computational chemistry, computational biology and drug molecules design. It researchs the relationship between structure and function at molecular level and is not limited by the sample preparation and test technical. So, it can provide more data reference and theoretical guidance for scientists. So, in this paper we mainly use computer molecular simulation technology to study how to improve the activity of IL-21from the following two aspects:(1) From the perspective of monoclonal antibody, our group have found that one monoclonal antibody called KJ can recognize cytokine IL-21specifically and enhance its biological activity. But, the other monoclonal antibody called KI has no effect on cytokine IL-21,which lays the important material foundation for studying the synergistic mechanism of monoclonal antibody. This paper embarks from the structure, to explore that KJ is how to enhance the activity of IL-21. we mainly use the computer molecular docking technology to design the complex structure of KJ(KI) docking with hIL-21, by comparison, we find that the binding sites of KJ and hIL-21is different from KI/hIL-21.By the dynamics analysis of Markov State Models, we also find that the structure of KJ/hIL-21is more stable than KJ/hIL-21, and the electrostatic interaction of KJ/hIL-21is stronger by the analysis of Transcomp.(2) From the perspective of hIL-21monomer, We are inspired by a piece of literature reported that the novel hIL-21analog exhibits a10-fold increase in potency in a cellular assay, so we obtain the3D structure of IL-21mutants (C2and C4) by MODELLER. Through the dynamics analysis of MSMs, we find that the mutants of C2and C4which were designed reasonably are more stable than WT hIL-21, and C2is more stable than C4, which proves that it will improve the activity of IL-21through mutation.