TY - JOUR
T1 - Comparative Analysis Molecular Simulation IL6R Alpha with TCZ and HIL6
T2 - Mechanism in Inflammatory Responses
AU - Merizka, Engla
AU - Wanandi, Septelia Inawati
AU - Bela, Budiman
AU - Widyaningtyas, Silvia Tri
AU - Fadilah, Fadilah
N1 - Publisher Copyright:
© 2024 Phcogj.Com.
PY - 2024/7
Y1 - 2024/7
N2 - 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.
AB - 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.
KW - Binding affinity
KW - HIL6
KW - IL6
KW - IL6R
KW - Molecular docking
KW - Molecular dynamics
UR - http://www.scopus.com/inward/record.url?scp=85203065256&partnerID=8YFLogxK
U2 - 10.5530/pj.2024.16.123
DO - 10.5530/pj.2024.16.123
M3 - Article
AN - SCOPUS:85203065256
SN - 0975-3575
VL - 16
SP - 738
EP - 743
JO - Pharmacognosy Journal
JF - Pharmacognosy Journal
IS - 4
ER -