Department of Chemical Sciences
School of Natural Sciences


January 31, 2014 at 2.30 pm in AG-80

Title : Understanding the Aggregation Properties of Amyloid Beta Through Solid State NMR and Designed Mutations

Abstract :

Zn+2 can alter the aggregation properties and toxicity of Amyloid beta (Aβ) by selectively precipitating out the soluble oligomers. What does it change? Using Solid State NMR on fibrils Aβ40 grown in the presence of Zn+2, we show that the turn region of the peptide is affected.  We have found that the fibrils of Aβ40 grown in the presence of equal concentration of Zn+2 has a similar hairpin shape but they differs in the turn region. However what we actually need to look at are the biologically active metastable oligomers, (not the fibrils) and focus on the turn region. Using a technique recently developed in the lab for looking at metastable structures, we find that the oligomers are different only in the turn and the terminal regions. This suggests that the conformational change starts at the two hydrophobic arms of the peptide. We are now trying to selectively disturb the stereospecific interaction in the nucleation centre by selective alternation of some amino acids in to their  "dextro" forms, which leaves chemical property of the peptide unchanged.

January 30, 2014 at 2.30 pm in AG-69

Title : to be announced

January 30, 2014 at 11.30 am in NMR Seminar Room

Title : Magic Angle Spinning NMR Studies of M218--60, VDAC, and bR

Astract :

In the last few years magic angle spinning (MAS) NMR has emerged as an important approach to examine the structure and function of membrane proteins. One of the primary advantages is that it enables studies of structure and function in native or quasi-native lipid environments, thus circumventing the perturbing effect of detergents which are often required for solution NMR experiments and crystallography. In addition, it has become possible to enhance the sensitivity of these experiments using dynamic nuclear polarization (DNP) by factors of ~100, thus facilitating more detailed structural studies. In this presentation we discuss the applications of MAS and DNP to three membrane proteins: M2 from influenza-A, the voltage dependent anion channel (VDAC), and bacteriorhodopsin. Studies of M218-60 indicate that this construct, which is fully functional, assembles as a dimer of dimers, rather a tetramer as seen in solution NMR and crystallographic studies. In addition, the amino-admantanyl drugs bind in the pore rather than on the surface. The structure, determined by a variety of dipole recoupling experiments shows that the His and Trp responsible for the H+ conduction are tightly packed M218-60 and that the transfer is likely an intermolecular process. We study VDAC in 2D crystals of DMPC and show that the protein perturbs the lipid gel®liquid crystalline transition, but that the protein does not change conformation dramatically in traversing this transition. We also delineate the structure of the N-terminal tail and show that it is situated in contact with the face of the β-barrel. Finally, we study the structure of photocycle intermediates of bR with DNP enhanced spectra and obtain evidence that bR could be a inward directed OH- pump rather than an outward directed H+ pump.

January 23, 2014 at 2.30 pm in AG-80

Title : Phosphorylation of an uv Inducible Protein (UVI31+) of Chlamydomonas reinhardtii

January 20, 2014, at 2.30 pm in AG69

 Seminar by Mr. Palas Roy

 Title: "Molecular Perspective to Photoinduced Processes in Organic Photovoltaics"

January 13, 2014 at 4.00 pm in AG-69

Title: Fibrils, membranes, crystals, sediments: solid-state NMR of large proteins

Abstract :

Solid-state NMR is an increasingly powerful tool to characterize challenging proteins. Notably, it can analyze an astonishing variety of states, as proteins inserted in membranes, crystals and simple sediments. Combined with other biophysical approaches, solid-state NMR thus gives unique insight into protein structure, and ultimately function. We will illustrate this with some recent examples from our laboratories, including the DnaB helicase from Helicobacter pilori, the BmrA ABC transporter, as well as the yeast prion fibrils Ure2p and Sup35p, for which we will show results related to sample preparation, sequential assignments and structural aspects.


January 6, 2014 at 4.00 pm in AG-69

Title : Luminescent Lanthanide Coordinated Probes for Sensing Signaling Phospholipids

December 26, 2013 at 11.30 am in NMR Conference Room

Title : Unraveling the Molecular Mechanism of the Peptide Aggregation by Characterizing the Invisible Intermediates Responsible for Alzheimer and Diabetics Diseases Using NMR Spectroscopy

Abstract :

The mis-folding and the subsequent aggregation of the peptide such as Abeta40 (40 amino acids) and hIAPP (37 amino acids) have been implicated in the pathogenesis of the diseases such as Alzheimer and Diabetics, respectively. Despite, the differences in the manifestation of the diseases, the underlying molecular mechanism of these disease follows a defined pattern. At the outset, the free peptide remains unstructured, but in the due course of time, the peptide oligomerizes into micellar structures, which elongates into long fibrillar structures. The long held belief that the fibrils are solely responsible for the lysis of the bio-membrane and the subsequent cell death, has been thwarted by the recent studies, which suggest that, it is the invisible, lowly populated, intermediate states of the peptides or oligomers, are responsible for the cell death. We used a series of NMR experiments such as CPMG (Carr Purcell Meiboom Gill spin echo)-relaxation dispersion experiment, DEST (Dark/invisible state exchange saturation transfer experiment) and Off-resonance NMR to understand the molecular mechanism of the initial stages of the aggregation of Abeta40 and hIAPP.


December 19, 2013 at 2.30 pm in AG-80

Title : Towards Nonlinear Label-Free Imaging of Monoamines in Live Vertebrates

Abstract :

Monoamines are an important class of neurotransmitters that act to transmit signals from one neuron to the next.  They play a significant role in the processing of emotion, reward, sleep-wake cycle and many different behaviors and imbalance of these neurotransmitters believed to be the cause of many neurodegenerative diseases like Parkinson’s, Alzheimer’s, Schizophrenia etc.  Direct imaging of monoamines by single photon excitation has proven to be difficult because their excitation resides in the ultra violet regions.  While some success has been obtained in imaging monoamine neurotransmitters by multi-photon excitation in cells and tissue, the holy grail will be to image it in vivo in live animals.  The present talk will describe our first attempts to use multi-photon label-free imaging to observe monoamine neurotransmitters in live vertebrates (zebra fish) and the corresponding instrumentation.


December 17, 2013 at 11.30 am in NMR Conference Room

Title : Protein Crystallography at SPring-8

December 16, 2013 at 4.00 pm in AG-69

Title : Nitric Oxide Reductases: Molecular Evolution of Respiratory Enzymes and Global Environment


Nitric oxide reductase (NOR) is an integral membrane protein that is involved in microbial denitrification, a type of anaerobic respiration in which nitrate is reduced in a stepwise manner to dinitrogen (NO3-→ NO2-→ NO → N2O → N2). In this process, NOR catalyzes the reduction of nitric oxide (NO), which is generated as an intermediate product in this process, to nitrous oxide (N2O) using two protons and two electrons (2NO + 2H+ + 2e- → N2O + H2O) via N-N bond formation and N-O bond cleavage at a binuclear center consisting of heme and non-heme iron (FeB). The product of the NOR-catalyzed reaction, N2O, is a greenhouse gas that is 310 times more powerful than carbon dioxide, and is also an ozone depleting substance. Since the use of nitrogen-based fertilizer increases global N2O levels by stimulating the action of soil denitrifiers, NOR is an important topic of study with respect to the global environment. NOR also has clinical and pharmaceutical importance, as evidenced by the fact that some pathogens use NOR to detoxify cytotoxic NO produced by macrophages in immune system of a host. In addition, it has been believed that NOR shares the same ancestor proteins as cytochrome c oxidase (CCO), which is an aerobic respiratory enzyme catalyzing the O2 reduction (O2 + 4H+ + 4e- → 2H2O) at a binuclear center consisting of heme and copper (CuB). Recently, we succeeded in structural determination of NOR in the resting, reduced and ligand-bound states. In the lecture, I will show the molecular mechanism of the NO reduction catalyzed by NOR, which was proposed on the basis of their molecular structures, and discuss the structural and functional characteristics of NOR in relation to the molecular evolution of the respiratory enzymes by comparing them with those of CCO.


December 16, 2013 at 11.30 am in AG-80

Title : Investigations of Thermal Properties of Carbon Nanotubes Using Ramen Spectroscopy and Molecular Dynamics Simulations

Abstract :

Single-walled carbon nanotubes are cylindrical tubes formed from covalently bonded carbon atoms and are described mathematically by performing a rolling operation on the honeycomb planar lattice of a single graphite layer. In the current study, we have examined closely the thermal expansion properties of these quasi one-dimensional objects using experimental Raman spectroscopy and Molecular Dynamics simulations. The Raman measurements have been performed employing a Thermo Scientific DXR spectrometer and a heated cell over a range of temperatures (27-200 deg C), while the Molecular Dynamics simulations utilize the powerful and versatile software package - Large-scale Atomic Molecular Massively Parallel Simulator (LAMMPS). Intriguing results from both experimental measurements and simulation studies help to shed new light on the thermal properties of carbon nanotubes and have important ramifications for their use in electronic devices.  

December 10, 2013 at 2.30 pm in AG80:

Title:Structure-function of dystrophin and utrophin in muscular dystrophy


Muscular dystrophy refers to a group of degenerative diseases that cause progressive muscle weakness. Duchenne/Becker muscular dystrophy accounts for more than half of all known cases. Symptoms that include constant falling, waddling, and outturned knees appear as early as age two. During the extreme phase, patients are unable to sit upright, move their arms or legs, or breathe on their own. Patients' life spans rarely exceed early to mid-twenties due to cardiac or respiratory failure. Genetic mutations in a vital muscle protein dystrophin trigger the disease. Utrophin is the closest homologue of dystrophin, and is being investigated as a possible replacement therapy to treat patients. In this talk, I will discuss the molecular mechanisms of the disease trigger and treatment at the fundamental protein level. Such knowledge will ultimately lead to the development of more effective therapies, which include engineered proteins and small molecules.

December 10, 2013 at 11.30 am in AG-80

Title : Role of Protectants and Denaturants in Polymers and Proteins: Insights from Computer Simulation



Longstanding mechanistic questions about the role of protectant Trimethylamine N- oxide (TMAO) which favors protein folding and the denaturant Urea are addressed by studying their effects on the folding of a model polymer chain. Using atomistic molecular dynamics simulations, we show that TMAO and Urea solutions act dramatically differently on these model polymer chains. Their behaviors are sensitive to the strength of the attractive dispersion interactions of the chain with its environment: when these dispersion interactions are high enough, TMAO suppresses the formation of extended conformations of the model polymer as compared to water, while urea promotes formation of extended conformations. Similar trends are observed experimentally on real protein systems. Quite surprisingly, we find that both protectants and denaturants strongly interact with the model polymer, seemingly in contrast with existing explanations of the effect on proteins. We show that what really matters for a protectant is its effective depletion as the polymer conformation changes, which leads to a negative change in the preferential binding coefficient, while the reverse is true in case of denaturant. Finally, we show our results on a simple model polymer is in reasonable agreement with a recent single molecule experiment on a synthetic polymer called polystyrene