Department of Chemical Sciences
School of Natural Sciences


May 13, 2014 at 2.30 pm in AG-69

Title :

Reshapint Amyloid Beta Aggregation Using Endogenous Proteins

May 12, 2014 at 4.00 pm in AG-69

Title :

Electron Transport Through Single Molecular Junctions: Molecular Wires, Switches to Energy Storage Devices

Abstract :

The idea of building electronic devices using single molecule as active component was first proposed by Aviram and Ratner in the early seventies. Indeed, molecules are of great interest for application in electronic devices because of their small size, their recognition properties, their ability of self-organization and their possibility of chemical modification and customisation. Thus, the ability to measure and control charge transport across metal/molecule/metal junction is of considerable fundamental interest and represents a key step towards the development of molecular electronics.

During my PhD, I have employed STM break junctions (STM-BJ) and a complimentary mechanically controllable break junction (MCBJ) technique to scrutinise the electron transport properties of metal/molecule/metal junctions under well controlled experimental conditions (in liquid at room temperature)1,2. Using these two experimental techniques, I will try to demonstrate the devise independence and reproducibility of the charge transport characteristics of metal/molecule/metal junctions. Due to the fact that, large number of measurements possible for STM-BJ and MCBJ techniques provides robust statistical analysis of the conductance data and shows clear evidence for the formation of molecular junctions. Many configurations can be sampled and characterized quantitatively by analyzing statistically significant number of conductance-distance and /or current-voltage traces. In addition to the conductance features, the characteristic length analysis of the conductance-distance traces provides additional information about the stability and evolution of molecular junctions. Using these expertise, we systematically studied correlation between molecular structure and conductance properties of metal/molecule/metal junctions formed with a family of thiol terminated oligo (phenylene ethynylene) (OPE) molecular wires (role of molecular length, conjugation, HOMO-LUMO gap, solvent)2,3and roll of anchoring group on single molecular junction conductance4. Furthermore, we also systematically studied the conductance switching of the pyridyl terminated dimethyldyhydropyrene photo chrome molecules upon visible light irradiation4.

Increase of the molecular length and/or of the HOMO-LUMO gap leads to a decrease of the single junction conductance of the linearly conjugated OPE molecules. The experimental data simulations suggest a non-resonant tunneling mechanism involving hole transport through the molecular HOMO, with a decay constant  Δ = (3.4 ± 0.1) nm-1 and a contact resistance Rc= 40kΩ per Au-S bond. Furthermore, decreasing the HOMO-LUMO gap by keeping the molecular length constant, we found that value of single molecular junction conductance was increasing. We also found effect of solvent on the single molecular junction conductances formed with mono thiol terminated OPE molecules. We also investigated the conductance properties of a photoswitchable dimethyldihydropyrene (DHP) derivative for the first time in single molecule junctions using the mechanically controllable break junction technique. We demonstrate that the reversible structure changes induced by photoisomerization of a single bis-pyridine-substituted DHP molecule are correlated with a large drop of the conductance value. We found a very high ON-OFF ratio (> 104) and an excellent reversibility of conductance switching5.

My present work is mainly focusing on modifying the Au, ITO, Pt electrode surfaces with functional molecules (electroactive or Photo active) and studying their properties at single molecule level under electrochemical conditions for molecular electronics and energy storage applications.


1.  Hong, W.J et al., Beilstein J. Nanotechnol. 2011. 2, 699-713.

2.  Kaliginedi et al., Journal of American chemical society. 2012, 134 (11), 5262–5275.

3.  Kaliginedi et al., Journal of American chemical society. 2014, in preparation.

4.  Moreno-Garcia et al., Journal of American chemical society. 2013, 135, 12228−12240.

5.  Roldan, D., Kaliginedi et al., Journal of American chemical society.  2013, 135, 5974-5977.

April 28, 2014 at 4.00 pm in AG-69

Title :

Elastic Network Model in describing equilibrium properties of proteins

Abstract :

In this talk, I will describe why elastic network model (ENM) is a faster alternative to standard molecular dynamics (MD) simulations in understanding the dynamics of proteins under equilibrium conditions. I will discuss the approaches taken for optimal parametrization of the model and how the parameters are used to study intrinsic flexibility of proteins. I will also talk about some future applications of ENM in studying specific functional motions of proteins.

April 22, 2014 at 2.30 pm in AG-69

Title :

Peptide Models of Lipid-protein Interaction and Protein Aggregation into Amyloids

Abstract :

Short peptides corresponding to the discrete protein modules offer an attractive system to study the structural and functional details of proteins and several biomolecular processes. We have exploited the manipulative versatility and design diversity offered by short peptides to address the phenomena of fatty acid acylation of proteins in context of their membrane association and of self-assembly of proteins into highly ordered amyloids aggregates. Our studies have shown that covalent modification of proteins with long chain fatty acid serves not just as lipid anchor but also as a regulator of the submembrane topology of the peptide chain. Using short peptides derived from the core sequences of amyloidogenic proteins, we have shown peptide concentration-dependent heterogeneity in amyloids aggregates and the existence of off-pathway aggregates. We have also probed the time-resolved tryptophan fluorescence intensity decay and have demonstrated that the immediate microenvironment of the indole moiety greatly influences the heterogeneity of the tryptophan lifetime distribution.

April 21, 2014 at 4.00 pm in AG-69

Title : 

Probing Plant Metabolism and Biomolecular Interaction: Studies by NMR

April 11, 2014 at 2.30 pm in AG-80

Title :

Molecular Machinery Involved in the Process of Small RNA Mediated Gene Regulation

Abstract :

Micro-RNA (miRNA) and small interfering-RNA (siRNA) are short (~22-nucleotide), single-stranded RNA molecules that regulate gene expression by promoting degradation or translational inhibition of target mRNAs. They influence diverse biological functions through the repression of target genes during normal development and pathological responses. A hallmark of small-RNA mediated gene silencing is a class of approximately 22-nucleotide RNAs that are processed from double-stranded RNA precursors by Dicer. The current model suggests that Dicer selects cleavage sites by measuring a set distance from the 3′ overhang of the double-stranded RNA terminus. Our structural studies on human Dicer in complex with siRNA having different overhang lengths at 5’- and 3’-ends along with in vitro and in vivo functional studies showed that Dicer recognizes both 3’- as well as 5’-ends for proper cleavage of siRNA/miRNA. The 5'-end recognition by Dicer, demonstrated for the first time by us, is important for precise and effective biogenesis of siRNA/miRNA. This study has provided practical benefits to the design of small-RNAs for gene silencing. We also solved the crystal structure of a large complex of Trax–translin heteromers, also known as C3PO, which has been proposed to activate the RNA-induced silencing complex by facilitating endonucleolytic cleavage of the siRNA passenger strand. Our studies establish that Trax adopts the translin fold, possesses catalytic centers essential for C3PO's endoribonuclease activity and interacts extensively with translin to form an octameric assembly. This study provides important insights into the catalytic mechanism of C3PO and its conserved role in human RISC activation. Just as miRNAs and siRNAs bind to the Argonaute proteins, another class of small RNAs encoded in the genome, the Piwi-interacting RNAs (piRNAs), that are 2′-O-methylated at their 3′ ends, bind to the Piwi proteins. Germline-specific piRNAs and Piwi proteins play a critical role in genome defense against transposable elements. Our work on Piwi proteins demonstrated the structural basis for piRNA 2'-O-methylated 3' end recognition by the PAZ domain of Piwi proteins.

April 10, 2014 at 4.00 pm in AG-80

Title :

Structural Insights into Non-vesicular Trafficking of Lipids by Lipid Transfer Proteins and Bacterial Toxin-Antitoxin Systems

Abstract :

Phosphorylated sphingolipid Ceramide-1-Phosphate (C1P) is a key regulator of cell growth, survival, migration and inflammatory responses, but non-vesicular mechanisms involved in its intracellular sensing, transfer and presentation remained unexplored till recently. We have identified a widely-expressed protein, CPTP (Ceramide-1-Phosphate Transfer Protein) in humans, which specifically transfers C1P. Our co-crystal structures established that C1P binding occurs via a surface-localized phosphate head-group recognition center connected to a hydrophobic pocket. Down-regulation of CPTP dramatically alters C1P steady-state levels, decreasing at the plasma membrane while elevating at the trans-Golgi where C1P is produced by ceramide kinase. The elevated C1P triggers proinflammatory eicosanoid generation associated with cellular inflammation, thus highlighting its physiological importance. We have also carried out structure-function studies on lipid transfer proteins involved in cell survival such as “accelerated cell death 11 (ACD11)” protein from Arabidopsis and “heterokaryon incompatibility C2 protein (HET-C2)” from the fungus Podospora anserina which has provided insights on roles of lipid transfer process in cell survival.

             Almost all bacteria and many archaea contain genes (encoding toxins) whose expression inhibit cell growth and may lead to cell death when overproduced, reminiscent of apoptotic genes in eukaryotes. These toxins are co-expressed and neutralized with their cognate antitoxins from TA (toxin-antitoxin) operons in normally growing cells. MazF (toxin) / MazE (antitoxin) system is one of the most extensively characterized TA systems. Under stress conditions, labile anti-toxins (MazE) are readily degraded by proteases allowing MazF (toxin) to cleave mRNA in a sequence specific manner. Recently, we solved the structure of Bacillus MazF in complex with ssRNA containing its target site as well as in complex with its cognate antitoxin MazE. This study has provided for the first time structural basis of recognition and cleavage of mRNA by MazF in a sequence specific manner during stress conditions and also demonstrated how antitoxin inactivates the toxin in normally growing cells.

April 7, 2014 at 4.00 pm in AG-69

Title :

Spectroscopic Studies of Interactions of Some Biologically Important Small Molecules with Proteins

Abstract :

Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms and participate virtually in every process within cells. The work is based on studies of the interactions of erythroid membrane skeletal protein, Spectrin and Hb along with serum protein from human (HSA) and from bovine (BSA) and another soluble protein of non-erythroid origin, the lysozyme (Lyz) with small organic molecules like the phosphate metabolite ATP, hemin and other small molecules of therapeutic importance e.g. 4-Nitroquinoline (4NQO), Merocyanine 540 (MC 540) and Imatinib mesylate. To study these interactions we have been using spectroscopic tools like absorption, fluorescence, circular dichroism, synchronous fluorescence, time-resolved fluorescence and theoretical modelling.

            SAs are the most important studied proteins in this field but the structural comparison between HSA and BSA was not studied previously.  This aspect has been highlighted in this thesis while discussing the interactions of MC 540 with both HSA and BSA. The discrepancies between the spectroscopic data obtained with HSA and BSA while interacting with MC 540 depict that although both the SAs have 80% structural similarities but the conformational flexibility is greater in HSA than that of BSA that has further been confirmed by the results obtained from time-resolved fluorescence and induced CD experiments. 

The Hb is the most studied blood protein and its structural changes have strong impact on blood-related or hematological diseases. In case of thalassemia, the prosthetic heme group of Hb is sometimes displaced from heme pocket. This type of phenomenon of heme loss could be stimulated in acidic pH. In erythrocyte cells, the membrane contains different types of phospholipids and cholesterol. Therefore, a detailed discussion on the impact of phospholipids on Hb has been done in my Ph. D. work. The heme loss and the release of oxygen from Hb occur simultaneously. The oxygen affinity of Hb decreases, in some diseased conditions as well as due to interaction with ATP. This aspect has been studied in detail by the spectroscopic techniques. Besides Hb, the Spectrin is also an erythrocyte membrane skeletal protein. The interaction of Spectrin with different phospholipids and drugs were studied previously. Here we have reported our findings regarding the interactions between Spectrin and an antileukemic drug, Imatinib as well as between Spectrin and another antileukemic as well as good fluorescent molecule, MC 540.     


March 24, 2014 at 4.00 pm in AG-69

Title :

'Turn On' Optical Probes for Sensing Manganese

March 20, 2014 at 2.30 pm in AG-80

Title :

Biophysical and Biochemical Studies on Structural characteristics of Plasmodium falciparum P2

March 10, 2014 at 4.00 pm in AG-69

Title :

Elucidating the Copper Binding Properties of Peptide Fragments of the CuA Center in Cytochrome c Oxidase

March 3, 2014 at 4.00 pm in AG-69

Title :

Photoinduced Electron Transfer in DNA Repair: A Computational Study

Abstract :

UV radiation (200-400 nm) causes damage of DNA, mostly producing the cyclobutane
pyrimidine and (6-4)-pyrimidine-pyrimidone (PP) photodimers. (6-4) photolyase is a DNA repair enzyme that selectively repairs (6-4)PP photodimer, using visible light. This repairprocess is a complex photocycle comprising of several electron transfer (ET) steps possibly coupled to proton transfer, controlled by the protein. The key repair steps are the forward electron transfer (FET) and the back electron transfer (BET) which involve the FADH−chromophore and the (6-4)PP. Experimentally, the ET rates of these steps have been estimated, but the overall repair mechanism remains elusive.

We wish to predict the ET rates with in the photolyase repair site and evaluate the roles of various factors that may influence these ET rates. Towards this, we have set up a multiscale computational apparatus based on a combination of QM, hybrid QM/MM and MD methodologies. With this approach, we have computed the energies of the FADH− - (6-4) PP (Donor-Acceptor) complex in different electronic states, formally describing the electron transfer reaction. We then evaluate the effects of the protonation state of key residues, the solvent and DNA counterions on these states and also account for the effect of the protein dynamics. Using these complex energy estimates, we predict the FET and BET rates employing the semi classical Marcus formalism and compare them against the experimental observations.

February 19, 2014 at 2.30 pm in AG-69

Title :

Characterization of the Non-Covalent Interactions of Propofol Using Mass Resolved Spectroscopy

Astract :

Propofol is probably the most widely used anaesthetic and became sadly famous several years ago as the cause of dead of the pop star Michael Jackson. The molecule exerts its action by docking on the GABAA receptors in the central nervous system. But why does it like to interact with the receptor, and how is its trip until it reaches the active site? Using a combination of laser spectroscopy and quantum mechanical calculations, under a reductionist approach, we will try to shed light on the forces that govern such odyssey.