In silico Identification and Computational Screening of Potential AFP Inhibitors Against Liver Cancer.

Area of Science:

• Biochemistry
• Computational Chemistry
• Oncology

Background:

• Liver cancer is a prevalent global malignancy, particularly in Asia and sub-Saharan Africa.
• Alpha-fetoprotein (AFP) is a key oncodevelopmental protein implicated in liver tumor formation.

Purpose of the Study:

• To identify potential inhibitors of alpha-fetoprotein (AFP) for liver cancer therapy.
• To evaluate natural compounds as novel therapeutic agents against liver cancer.

Main Methods:

• Hybrid approach combining virtual screening, pharmacophore generation, and molecular dynamics (MD) simulations.
• Two-dimensional similarity searches and molecular docking were employed to screen anti-cancer and natural compound libraries.
• Analysis of binding energies, affinities, and interactions with AFP residues.

Main Results:

• Identified top-ranked compounds with high binding affinity and low binding energy against AFP.
• Key interacting residues (e.g., Leu-219, His-222, Lys-242) within AFP were pinpointed.
• Compound NC002 demonstrated potent inhibitory activity against AFP in MD simulations, PCA, and MM-GBSA analyses.

Conclusions:

• The natural compound NC002 shows significant potential as an effective inhibitor of AFP.
• NC002 represents a promising candidate for the development of novel liver cancer therapeutics.
• Computational analyses confirm NC002's efficacy in targeting AFP for potential liver cancer treatment.