EMAN RESEARCH PUBLISHING | Journal | <p>Molecular dynamics simulation and <em>in silico</em> binding study of CBS and IL17A outline modulation of tumor microenvironment</p>
System and chemical biology
RESEARCH ARTICLE   (Open Access)

Molecular dynamics simulation and in silico binding study of CBS and IL17A outline modulation of tumor microenvironment

Md Shamsuddin Sultan Khan A*, Aman Shah Abdul Majid B, Amin Malik Shah Abdul Majid B

+ Author Affiliations

Advanced Bioinformatics & Chemistry 1(1) 006-018 https://doi.org/10.25163/abc.11206611721300819

Submitted: 17 May 2019  Revised: 21 July 2019  Published: 30 August 2019 

The tumorigenic reactions were more serious due to senescence of the tumor in the reaction of IL17A, CBS and MHCII molecules. 

Abstract


Elevated levels of intratumoral interleukin 17A (IL17A) and the transulfuration metabolic enzyme cystathione beta synthase (CBS) can elicit T cell-mediated tumor synergy for tumor antigen. In vitro cellular analysis and in vivo extotopic xenograft study were conducted to determine the tumor synergy of CBS-IL17A-MHCII. Various computational simulation packages were used to simulate the binding dynamics of T cell mediated epitopes of tumor antigens (ETA) with the major histocompatibility complex II (MHCII). Simulation studies suggested that ETA work as immunodominant components by concentrating binding affinity to the MHCII in the presence of IL17A and CBS. 98% of ETA had lower binding energies for the protein combination (CBS-IL17A-MHCII) compared to other combination (IL17A-MHCII) and single protein (MHCII), which revealed synergistic binding activity to MHCII molecules in the presence of CBS and IL17A. Furthermore, the inflammatory and angiogenic cytokines were simultaneously increased after CBS-IL17A-MHCII treatment in compared to MHCII and caused the ETA reaction to be more serious. In this study, we identified the synergy of the CD4+ T-cells ETA with the (MHCII) due to synergy of IL17A and CBS reactions. In conclusion, the tumorigenic reactions were more serious due to senescence of the tumor in the reaction of IL17A, CBS and MHCII molecules.

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