Molecular Docking, Molecular Dynamics Simulation, and Pharmacophore-Based Virtual Screening Unveil Natural Compounds
Abdulrahim A Alzain1, Mohammed A Almogaddam1, Rayan Yousif1
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Gezira, Wad Madani 21111, Sudan.
Introduction:
The aberrant expression of T cell immunoglobulin mucin-3 (TIM-3) has been linked to adaptive immunotherapy resistance and poor prognosis. Targeting TIM-3 has gained popularity due to positive outcomes in preclinical settings.
Materials And Method:
This research explored the Supernatural 3.0 database for potential TIM-3 inhibitors. A pharmacophore-based virtual screening, molecular docking, and molecular dynamics simulations were conducted for 449,008 compounds. Compounds SN0085417 (-7.542 kcal/mol), SN0261906 (-7.036 kcal/mol), and SN0276180 (-6.871 kcal/mol) showed better docking scores. These compounds revealed remarkable hydrogen bonds and π-π stackings interactions with TIM-3 IgV domain.
Results:
The analysis of root-mean-square deviation (RMSD) and root-meansquare-fluctuation (RMSF) trajectories displayed stable interaction patterns with no substantial conformational changes in the TIM-3 backbone.
Conclusion:
These findings proposed SN0085417, SN0276180, and SN0261906 as TIM-3 inhibitors, which, with more extensive analysis, could undoubtably add to the realm of feasible TIM-3 based cancer immunotherapies.
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