My research is focused on the development of computational models to predict the mechanism, dynamics, reactivity and selectivity in organic and polymer chemistry reactions.
I am mainly involved in five areas of research:
- Computational studies of transition metal-catalyzed reactions. Performed mechanistic studies with quantum mechanical calculations to first-time investigate the mechanism and reactivities of Cu-catalyzed atom transfer radical polymerization (ATRP), and Rh-catalyzed enantioselective atom transfer radical addition (ATRA), as well as Cu/Rh-catalyzed olefin functionalization. Collaborators: Prof. Matyjaszewski at CMU, Prof. Ready at UT Southwest, Prof. Buchwald at MIT, and Prof. Dong at UChicago.
- Computational studies of photoredox reactions. Predicted the mechanisms for photoredox catalyst-induced reactions with DFT and Marcus Theory calculations. Collaborators: Prof. Matyjaszewski at CMU, and Prof. Wang at UAlbany.
- Development of predictive models for catalyst reactivities. Established multivariate linear regression to predict catalyst reactivities for Cu-ATRP with stereoelectronic descriptors obtained from DFT. Built catalyst-substrate interaction models to decompose the total transition state energy into chemically meaningful energy terms and thereby to analyze the origin of reactivities and selectivities.
- Molecular dynamics simulations of chemical reactions. Analyzed the bifurcation trajectory for alkyne hydroboration reaction with ab inito MD simulation. Investigated the conformation effect of cis- and trans-macrocyclic olefins on their reactivity difference with Ru catalyst with force-field MD simulation and DFT calculations. Collaborators: Prof. Curran and Prof. Meyer at UPITT.
- Computational studies ofdrug compounds. Performed DFT calculations to investigate the mechanisms of covalent bond formation between Benzothiazionones (a tuberculosis drug candidate) and cysteine in protein DprE1. Investigated the regio- and stereo- selective functionalization of bioactive compounds such as anticancer agent Bryostatins and carbohydrate with conformational sampling and DFT calculations. Collaborators: Prof. Wender at Stanford, and Prof. Zhu at UToledo
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.