My research has been focused on the application of molecular modeling and cheminformatics approaches to drive drug design and discovery.
I have been mainly involved in four areas of research:
- Structure-based drug discovery. Built computational models for multiple domain protein Sequestosome-1/p62 with homology modeling and MD simulation. Implemented off-target predictions on FDA-approved anti-osteoporosis drugs via high-throughput molecular docking. Unveiled structural determinants for selective inhibition against CDK9 and other CDKs with sequence and protein alignments and molecular docking.
- Ligand-based drug discovery. Developed the first 3D-QSAR pharmacophore model for CDK9 inhibitors. Performed pharmacophore-based virtual screening and scaffold-hopping to discover novel CDK9 inhibitors. Performed 2D-similarity search via ChEMBL, DrugBank. SuperTarget, BindingDB databases to predict off-targets for FDA-approved anti-osteoporosis drugs.
- Chemical library design and analysis. Analyzed the novelty and diversity of chemical library using BCUT-defined chemistry space partition and 2D similarity calculation. Built a virtual “focused” library of bioactive compounds from traditional Chinese medicine for discovery of novel anti-diabetic leads via virtual screening (collaborated with Novo Nordisk). Built a virtual combinatorial library from representative CDK9 lead compounds for virtual screening to prioritize compounds for synthesis.
- Synthetic medicinal chemistry. Designed, synthesized, and performed the SAR analysis for the compounds against CDK9.