Computational Chemistry Lead

Small molecule drug discovery for RNA targetsNMR data acquisition and analysisDetermination of ensemble structures of targets in atomic resolutionDesign and screening of a fluorine fragment library by NMRStructural biology and cheminformatics analysis of ensemble docking dataIn vitro binding assays and characterization of identified hitsDeveloping an automated de novo design and lead generation method

Led a team of six scientists to accomplish the following missions: expression and purification of target proteins, compound library management, virtual screening, identification of fragment hits to enable fragment-based drug discovery (FBDD), building and screening in-house DNA-encoded libraries, characterization of ligand-target interaction by using NMR, SPR, MST, DSF, ITC, LC/MS, and X-ray crystallography.Led a first-in-class FBDD drug discovery project for a colorectal cancer targetPerformed molecular modeling for hit-to-lead and lead optimization of multiple projectsTroubleshot NMR analysis of discovery and development compoundsDeveloped and serviced a web-based compound database and cheminformatics decision support tools

Determined dynamic ensemble structures of target RNAs and identified hits in the multiple in-house and collaborative projects. Co-authored an awarded fast track SBIR grant on NMR chemical shift prediction technologyCo-authored a pending patent about determining 3D nucleic acid structures using specially isotope-labeled oligonucleotides samples and NMR chemical shift dataDeveloped softwares written in C++ and Python for prediction and calculation of NMR data (chemical shift, J coupling and RDC), selection of ensemble structures from MD trajectories, analysis of molecular docking scores and poses

Developed a novel algorithm to accurately predict rotational tumbling time of intrinsically disordered proteins (IDPs), which provides a quantitative tool to detect residual domain structure in the IDP and regulatory switches within interdomain linkers of multi-domain proteins Investigated and compared protein backbone dynamics of the wild-type, disease-­prone, and disease-resistant prion proteins and revealed their undifferentiated dynamic behaviors in picosecond to nanosecond time scaleStudied excited low populated states of dihydrofolate reductase (DHFR) by combining NMR residual dipolar couplings (RDCs) and R2 relaxation dispersion and demonstrated that the structure of a less than 5% populated otherwise invisible state can be determined

Investigated an effect of supercoiling on local structure and dynamics of a DNA site by using NMR and fluorescence resonance energy transfer (FRET) and showed that a supercoiling responsive DNA segment that has a critical role in DNA replication are more susceptible to such global constraint than other closely related DNA sequencesMentored 6 graduate studentsCo­-authored multiple awarded research grants