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
D. Thirumalai and S.A. Woodson. Kinetics
of folding of proteins and RNA. Acc. Chem. Res. 29, 433-43
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.
ideas on the molecular basis of protein and peptide aggregation. Curr.
Opin. Struct. Biol. (2003)