Comparative Analysis Molecular Simulation IL6R Alpha with TCZ and HIL6: Mechanism in Inflammatory Responses

Abstract

Introduction: In cases of inflammation, there is typically a connection between IL6R and HIL6. If there is an excessive level of activity in this connection, it can lead to a cytokine storm. Tocilizumab (TCZ), also known as AntiIL-6R, is a biologic drug that is a recombinant humanized monoclonal antibody. It is specifically used to treat inflammatory and autoimmune diseases that are associated with cytokine storms. Method: This study utilizes in silico analysis to assess the ability of TCZ, a biosimilar, to block IL6R and compares it to the blocking effect of HIL6. Validation of the 3D structure of the IL6R was performed using a Ramachandran plot. Results: The IL6R alpha subunit had a validation score of 97.86%, while the IL6R beta subunit had a validation value of 95.54%. The molecular docking analysis reveals that the TCZ light chain forms a complex with IL6R, yielding a docking score of -16.4 kcal mol-1. Similarly, the TCZ heavy chain also interacts with IL6R, resulting in a docking value of -15.5 kcal mol-1. Notably, both scores are higher than the docking score of the control, which involves IL6R with HIL6, measuring -12.5 kcal mol- 1. The root mean square fluctuation (RMSF) value of the IL6R protein in the presence of TCZ (Tocilizumab) is consistently below 2, with an average range of 0.04-0.09. Conclusion: The affinity between IL6R and TCZ is greater than the affinity between IL6R and HIL6. Keywords: Binding affinity, IL6, IL6R, HIL6, Molecular docking, Molecular dynamics.