Debananda Das, Ph.D.
Dr. Das's current research interests are as follows: 1) prediction of affinity of small molecule inhibitors against proteins with resistant mutations, 2) interaction of small molecule inhibitors with CCR5, and 3) virtual screening to identify a new class of inhibitors.
1) structure-based discovery and design of small molecule inhibitors, 2) virtual screening for small molecule lead identification, 3) anti-HIV inhibitors, 4) structure-function relationships, 5) computational structural biology and computational chemistry
Dr. Das's current research interests are as follows:
1. Prediction of affinity of small molecule inhibitors against proteins with resistant mutations: The prediction of activity of a new inhibitor against mutant proteins is important in light of drug resistance in several diseases including AIDS and cancer. More reliable predictions of the binding affinity of inhibitors against proteins with drug-resistant mutations would be of use in the design of novel and more potent inhibitors. We are working on improving the performance of current free energy of binding algorithms with improved treatment of solvation and electrostatics to more accurately determine the binding free energies of newer potential inhibitors.
2. Interaction of small molecule inhibitors with CCR5: We had built a robust model of the interaction of CCR5 with its inhibitors. Over the years we have made improvements to our original model to rationalize new experimental data. We are currently working on deducing structural interactions of several new classes of inhibitors with CCR5. The structure-to-activity relationships deduced by our models help in the future design and synthesis of inhibitors with improved potency and properties. 3. Virtual Screening to identify new class of inhibitors: We are applying virtual screening techniques in identifying new class of inhibitors against well validated cellular and viral targets of HIV.
GRL-04810 and GRL-05010, difluoride-containing nonpeptidic HIV-1 protease inhibitors (PIs) that inhibit the replication of multi-PI-resistant HIV-1 in vitro and possess favorable lipophilicity that may allow blood-brain barrier penetration.Antimicrob. Agents Chemother.. 57: 6110-21, 2013. [ Journal Article ]
GRL-0519, a novel oxatricyclic ligand-containing nonpeptidic HIV-1 protease inhibitor (PI), potently suppresses replication of a wide spectrum of multi-PI-resistant HIV-1 variants in vitro.Antimicrob. Agents Chemother.. 57: 2036-46, 2013. [ Journal Article ]
P2" benzene carboxylic acid moiety is associated with decrease in cellular uptake: evaluation of novel nonpeptidic HIV-1 protease inhibitors containing P2 bis-tetrahydrofuran moiety.Antimicrob. Agents Chemother.. 57: 4920-7, 2013. [ Journal Article ]
- Expert Opin Emerg Drugs. 17: 135-45, 2012. [ Journal Article ]
Loss of the protease dimerization inhibition activity of tipranavir (TPV) and its association with the acquisition of resistance to TPV by HIV-1.J. Virol.. 86: 13384-96, 2012. [ Journal Article ]
Dr. Das obtained his M.S. in chemistry from the Indian Institute of Technology, Kanpur, in 1991, and a M.Tech. in chemical analysis from the Indian Institute of Technology, Delhi, in 1994. Working with Prof. Scott Whittenburg, he earned his Ph.D. in chemistry from the University of New Orleans in 1999, where he carried out computational studies on the structure of small molecules. He carried out his postdoctoral work on QM/MM methods and applications in the group of Dr. Bernard Brooks at NIH. In 2002, he joined Tripos, Inc., as an application scientist. He joined the HIV and AIDS Malignancy Branch (HAMB) at NCI in 2005. At HAMB, he works in a multi-disciplinary environment focusing on the design, synthesis and development of the next-generation of therapeutic agents against HIV and HIV-associated malignancies.