Molecular Docking and Dynamics Analysis of Tofacitinib Binding to JAK1: Implications for Autoimmune Disorder Therapy

This study explores Tofacitinib’s interaction with Janus kinase 1 (JAK1), crucial for its therapeutic potential in autoimmune disorders like rheumatoid arthritis (RA). Through molecular docking and molecular dynamics (MD) simulations, we identified strong binding affinity between Tofacitinib and JAK1, with a binding energy of -7.7 kcal/mol, stabilized by hydrogen bonds, hydrophobic interactions, and van der Waals forces within the ATP-binding pocket. The binding conformation remained stable over 100 nanoseconds of MD simulation, with RMSD values between 1.5 to 2.5 Å, confirming the drug's selectivity and minimal off-target effects. Binding free energy calculations (MM/GBSA) further validated this interaction, showing a favorable energy of -30.2 kcal/mol, driven primarily by hydrophobic and electrostatic forces. These findings are consistent with existing literature, showing that Tofacitinib works well as a JAK1 blocker. Clinically, the stability and selectivity of Tofacitinib’s binding to JAK1 indicate its potential to improve treatment options for autoimmune diseases by enhancing therapeutic efficacy and reducing off-target effects, which could lead to more tailored and safer treatment strategies. The study provides a basis for future exploration of Tofacitinib’s interactions with other JAK isoforms and the development of next-generation JAK inhibitors with enhanced efficacy and safety.