Virtual Screening of Small Molecules Targeting BCL2 with Machine Learning, Molecular Docking, and MD Simulation

Abstract

This study aimed to identify potential BCL-2 small molecule inhibitors using deep neural networks (DNN) and random forest (RF), algorithms as well as molecular docking and molecular dynamics (MD) simulations to screen a library of small molecules. The RF model classified 61% (2355/3867) of molecules as ‘Active’. Further analysis through molecular docking with Vina identified CHEMBL3940231, CHEMBL3938023, and CHEMBL3947358 as top-scored small molecules with docking scores of −11, −10.9, and 10.8 kcal/mol, respectively. MD simulations validated these compounds’ stability and binding affinity to the BCL2 protein.

Keywords

• small molecules
• virtual screening
• BCL2
• cancer therapeutics