Virtual Screening and Molecular Dynamics Studies of Phytochemicals Targeting Ran GTPase: Identification of Potential...

Area of Science:

• Oncology
• Computational Chemistry
• Pharmacology

Background:

• Ran GTPase is crucial for cell fate and often overexpressed in cancers via PI3K/Akt and ERK/MEK pathways.
• Targeting Ran GTPase is vital for minimizing cancer cell metastasis due to limited specific drugs.

Purpose of the Study:

• To identify novel molecules inhibiting Ran GTPase activity for potential cancer therapy.
• To explore natural compounds as therapeutic agents against Ran GTPase.

Main Methods:

• Virtual screening of the SuperNatural database using the Schrödinger platform.
• Molecular docking, 100 ns molecular dynamics simulations, and DFT-based electronic structure analysis (FMO, MEP).
• ADME/Toxicity profiling to evaluate pharmacokinetic properties and safety.

Main Results:

• Ten natural compounds exhibited strong binding affinity to Ran GTPase (docking scores -13.85 to -10.48 kcal/mol).
• Three compounds (CID_11194, CID_16220, CID_6220) showed high stability in molecular dynamics simulations.
• CID_11194 and CID_16220 demonstrated favorable, non-toxic pharmacokinetic profiles, with CID_16220 identified as a potential breast cancer therapeutic candidate.

Conclusions:

• Virtual screening successfully identified potent natural inhibitors of Ran GTPase.
• Compound CID_16220 exhibits promising therapeutic potential for breast cancer treatment due to its efficacy and safety profile.
• Further investigation into CID_16220 is warranted for its clinical application in oncology.