I research structure-function of macromolecules and drug discovery. I also study cancer and diabetes related kidney disease currently targeted for drug discovery. Tools used are x-ray crystallography electron microscopy, biochemical and medicinal chemistry related.
Nearly every major process in a cell is carried out by a complex assembly of several proteins. The main focus of the lab involves understanding the structural organization requirements by multiple protein assemblies to facilitate biological function. Our approach is to use a multidisciplinary cycle to study the structure-function relationship of proteins. We also use structure-based drug and protein design to develop novel therapeutics against cancer, Alzheimer’s disease and microbial infections. Biophysical tools such as x-ray & neutron crystallography, molecular modeling, CD, MS, fluorescence spectroscopy and ultracentrifugation are the techniques used in our lab.
Specifically, my research focuses on three areas of interest. They are:
- The structure-function and regulation of ribonucleotide reductase (RNR) by small molecule effectors and its protein inhibitor, the Suppressor of Mec 1 Lethality 1 (Sml1).
- The structure-function of pathogenic amyloid forming proteins.
- The investigation of enzyme catalytic mechanisms, dynamics and solvent structure of macromoleculesusing neutron and ultra-high resolution x-ray diffraction.
We use structural and biochemical tools to interrogate biological function such as allosteric regulation of macromolecules. The lab uses structural, knowledge-based in silico tools for developing drugs against diseases such as cancer, Alzheimer’s and kidney failure. In a second front, neutron diffraction and ultrahigh resolution x-ray diffraction is used to investigate transition states of catalytic mechanisms, solvent structure and dynamics. Our lab uses biochemical, biophysical and structural tools such as x-ray diffraction, neutron diffraction, electron microscopy, isothermal titration calorimetry and spectroscopy to unravel the mysteries of life.