Download Mahua Ghosh - SN Bose National Centre for Basic Sciences

Mahua Ghosh
Research Scientist
[email protected]
Dr. Mahua Ghosh received her PhD from TIFR, Mumbai. She then
worked as a postdoctoral researcher at Ontario Cancer Institute,
Canada, and NIEHS, National Institute of Health, USA, before joining
I.I.S.E.R Kolkata as an Assistant Professor. She has been at Satyendra
Nath Bose National Centre for Basic Sciences since 2010.
ž My research interests primarily involve understanding of
the molecular basis in biological system by their biophysical,
structural and functional characterizations. Quantitative
experimental and computational studies on Protein-protein,
protein-ligand, lipid-protein interactions
1. A state of the art fully functional and self-sufficient “Protein
Expression and Purification” facility is developed in the
Centre. Many proteins of bacterial origin related to
multidrug resistance activity have already been expressed,
purified and characterized.
2. We show that the thermodynamics of metal ion induced
conformational changes aid to understand the functions
of protein complexes. This is illustrated in case of a
metalloprotein, alpha-lactalbumin (aLA), a divalent metal
ion binding protein. We use the histograms of dihedral
angles of the protein, generated from all-atom molecular
dynamics simulations, to calculate the conformational
thermodynamics. The thermodynamically destabilized and
disordered residues in different conformational states of
a protein are proposed to serve as binding sites for ligands.
This is tested for b-1,4-galactosyltransferase (b4GalT)
binding to the Ca2+-aLA complex where the binding
residues are known. Among the binding residues, the Cterminal residues like aspartate (D) 116, glutamine (Q) 117,
tryptophan (W) 118 and leucine (L) 119 are destabilized
and disordered and can dock b4GalT onto Ca2+-aLA.
No such thermodynamically favourable binding residues
can be identified in case of the Mg2+-aLA complex. We
apply similar analysis to oleic acid binding and predict that
the Ca2+-aLA complex can bind to oleic acid through the
basic histidine (H) 32 of A2 helix and the hydrophobic
residues, namely, isoleucine (I) 59, W60 and I95 of the
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SNBNCBS Annual Report 2014 -15
interfacial cleft. However, the number of destabilized and
disordered residues in Mg2+-aLA is less, and hence, the oleic
acid binding to Mg2+ bound aLA is less stable than that to
the Ca2+-aLA complex. Our analysis can be generalized to
understand the functionality of other ligand bound
proteins.
3. We looked into the stability of coordination of metal ion
into the metal ion binding pocket of an EF-hand protein
by quantum chemical calculations.
Future Plan
The following projects are undertaken:
ž Biophysical characterization and antibiotic interactions of
a bacterial yfdX protein from S.Typhi, STY3178 using
fluorescence, CD and NMR.
ž Chemical denaturant induced unfolding and stability of
STY3178 using CD, fluorescence and NMR.
ž Reversible thermal folding of STY3178 using CD,
fluorescence and computational methods.
ž Sequence specific resonance assignments of STY3178 using
heteronuclear triple resonance NMR experiments.
ž Divalent ion induced changes in STY3178 using CD,
fluorescence, mass spectrometry and MD simulations.
ž SDS induced conformations of small heat shock protein
HspH and its chaperonic activity.
ž Protein-Protein interaction of beta barrel membrane protein
STY3179 with soluble yfdX protein STY3178.
ž Prediction the missing protein fragment conformation
using conformational thermodynamics approach for
Tropinin C a calcium binding EF hand protein.
Publications in Journals
1. Samapan Sikdar, J. Chakrabarti and Mahua Ghosh, A
microscopic insight from conformational thermodynamics
to functional ligand binding in proteins, Molecular
BioSystems, 10, 3280-3289 (2014)
2. Samapan Sikdar, Mahua Ghosh, Molly De Raychaudhury
and J. Chakrabarti, Quantum chemical studies on the role of
residues in calcium ion binding to Calmodulin, Chem Phys
Lett, 605-606, 103-107(2014)
Supervision of Students
Ph.D. Students: Paramita Saha and Samapan Sikdar
Project Student: Kathakali Sarkar from Department of
Biotechnology, St. Xavier’s College, Kolkata
Sponsored Projects
1. “Structural and Functional Characterization of small Heat
Shock Proteins from Bradyrhizobium japonicum” in the
subject area of Life Sciences, funded by DST, Government
of India.
2. “Microscopic calculations of metal ion binding to proteins”
in the subject area of Physical Sciences, funded by DST,
Government of India.
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