Professor Thirumalai won the Presidential Young Investigator Award in 1987. His current research interests are in the general area of Biophysical Chemistry. The problems he is focusing on include folding of biomolecules and shape changes in DNA molecules under equilibrium and non-equilibrium conditions.  A grand challenge in molecular biology is to understand how biomolecules (proteins and RNA) reach their functional native states starting from an astronomical number of random coil conformations. The understanding of how this process occurs impacts on the design of biomolecules of specified topology, and can offer clues to understanding diseases caused by conformational defects such as prions. His research group is focussed on discovering general principles that govern folding of biomolecules. They use a combination of theoretical and computational strategies to answer several questions. In particular, they are interested in (a) the effect of mutations on stability of proteins; (b) folding mechanisms of large RNA molecules; (c) causes of misfolded conformations in proteins; (d) variations in the folding mechanisms of proteins in response to changes in environment; (e) role of chaperones in aiding protein folding (in collaboration with G.L. Lorimer in the Department of Biochemistry).  The other area of interest is in the study of changes in DNA shapes doe to stretching and condensation. Currently, it is possible to manipulate single DNA molecules using optical tweezers. Such experiments provide direct measurements of the extension of DNA subject to force. The reversible condensation and stretching of DNA which are important steps in the replication process, is being studied using statistical mechanical models. Such studies will provide detailed microscopic description of collapse of DNA and other synthetic polyelectrolytes and polyampholytes.  Selected Publications: D. Thirumalai and S.A. Woodson. Kinetics of folding of proteins and RNA. Acc. Chem. Res. 29, 433-43 (1996). H. Orland and D. Thirumalai. A kinetic model for chaperonin assisted folding of proteins. J. Phys. Chem. (France) I 7, 553-560 (1997). B.-Y. Ha and D. Thirumalai. Semiflexible chains under tension. J. Chem. Phys. 106, 4243-4247 (1997). D.K. Klimov and D. Thirumalai. Lattice models for proteins reveal multiple folding nuclei for nucleation-collapse mechansim. J. Mol. Biol. 282, 471-492 (1998). D. Thirumalai, D.K.Klimov and R.I.Dima.  Emerging ideas on the molecular basis of protein and peptide aggregation. Curr. Opin. Struct. Biol. (2003)