TIFR
Department of Chemical Sciences
School of Natural Sciences

Calender

December 2, 2014 at 2.30 pm in AG-69

Title :

Mechanistic Investigation of Membrane Fusion through a Model Caged SNARE Protein

Abstract :

Intracellular membrane fusion is directed by the formation of a specific complex of proteins such as SNARE [Soluble NSF (N-ethylmaleimide-sensitive factor) Attachment Protein Receptor]. There are several mechanisms of SNARE mediated membrane fusion, but the exact nature of these processes remains debated. In particular, little is understood about the molecular mechanisms governing trans-SNARE complex nucleation and zippering in driving fusion. Assembly strength and fusion kinetics in these systems are highly complex, and the downstream events of membrane contact (docking), stalk formation, hemifusion, and fusion pore opening along the fusion pathway is still unclear. Moreover, the exact role of the transmembrane domain (TMD) of synaptobrevin and syntaxin-1A is unknown. In this presentation, I will demonstrate light triggered mechanistic investigation of membrane fusion using artificial caged SNAREs. Caging of a biologically active molecule with a photolabile protecting group at a key functional position can temporarily mask the functionality and inactivate the biomolecule. The activity of the molecule can be restored by uncaging, externally triggered by light of appropriate wavelength. However, caging group strategy has not been applied yet to temporarily block the membrane fusion activity of SNARE protein to get deeper structural insights into the SNARE zippering and assembly pathway. I will illustrate the design of artificial caged SNAREs with photolabile protecting groups to dissect the mechanism of SNAREs in membrane docking, hemifusion, and fusion. I will also provide a method to arrest and study the intermediates such as partially zipped trans-SNARE complexes which is used for light triggered stepwise recognition/two-stage zippering of membrane fusion. Our recent findings of light triggered membrane fusion using artificial caged SNAREs can be a significant starting point to address many compelling questions surrounding the topic of SNARE-induced membrane fusion.

At the end, I will present my future research proposal: 1) Synthetic Transmembrane Peptide-Based Ion Channel and 2) Synthetic Molecular/Supramolecular Machines.

December 1, 2014 at 4.00 pm in AG-69

Title :

Manipulation of Membrane Structure and Function Using Light

Abstract :

The 1st part of my presentation will focus on light triggered mechanistic investigation of membrane fusion using artificial caged SNAREs [Soluble NSF (N-ethylmaleimide-sensitive factor) Attachment Protein Receptor]. Membrane fusion is a fundamental process in life and plays a key role in exo- and endocytosis, fertilization, intracellular trafficking, enveloped virus infection, etc. All intracellular membrane fusion is directed by the formation of a specific complex of proteins, such as SNARE. Two SNARE proteins residing in the plasma membrane are syntaxin-1A (Sx) and SNAP-25. A SNARE protein residing in the membrane of synaptic vesicle is synaptobrevin (Syb). The SNAREs assemble into four-α-helix bundles. There are several mechanisms of SNARE mediated membrane fusion, but the exact nature of these processes is still unknown. I will demonstrate the design of artificial caged SNAREs using photolabile protecting groups to temporarily mask the functionality of the recognition site with the goal of obtaining deeper structural insights into the SNARE-mediated membrane fusion mechanism.

In the 2nd part of my presentation, I will illustrate how an understanding of membrane events can be used to promote drug molecules at tumor sites by passive and active targeting to tumor. Another goal is to target local pH of tumor site. A tumor microenvironment (cytosol) usually has a pH of 6.5-7.2, an endosomal pH of 5.0–6.0 and a lysosomal pH of 4.0−5.0, which is different from the normal tissues pH of 7.4. This pH gradient is of particular importance, since several drugs and carriers for cancer therapy are internalized through endocytosis and trapped within endosomal and lysosomal compartments. I will explain NIR pH switchable liposomal formulation where laser-induced photothermal heating is turned on at acidic pH (> 6.5) and turned off at physiological pH 7.4 which could show major toxic effects against tumors, without causing damage to normal cells. Drug release from thermosensitive liposome will be demonstrated using logical application of pH and photothermal heating. This liposomal formulation with laser could be a promising strategy for ‘Photothermal Cancer Theranostics’.

November 24, 2014 at 4.00 pm in AG-69

Title

Development of spectral simplification methods in NMR spectroscopy

Abstract :

Importance of NMR spectral simplification methods for unambiguous structural determinations of small organic molecules in solid and solution-state will be discussed. The development of solid-state NMR experimental techniques are aimed for obtaining desired spectral information, both scalar and dipolar couplings (inter nuclear distances), by simplifying complex NMR spectra.  Whereas, in solution-state all the anisotropic interactions average to zero, thereby yield NMR spectra representing only the features of chemical-shift and scalar (J) couplings.  However, often the solution-state 1H NMR spectra suffer from intense overlaps due to spread of J-multiplets. In solution-state, the enhanced spectral resolution has been accomplished by employing new real-time pure-shift pulse schemes that involve broadband and band-selective homodecoupling. 

 

November 21, 2014 at 2.30 pm in AG-69

Title :

 Change of Protein Conformation and Function Associated with Amyloid Aggregation

November 17, 2014 at 4.00 pm in AG-69

Title :

Probing Energetic and Spatiotemporal Heterogeneity using Single-Emitter Spectroscopy

Abstract :

While ensemble measurements have been extremely successful in understanding the structure and dynamics in the condensed phase, they have often failed to capture the underlying details of the physical processes which give rise to the observed “bulk” behaviors. In this context, single-molecule fluorescence microscopy has emerged as a valuable technique to extract information regarding local (nanoscale) properties in complex (disordered) systems and understand the extent of spatiotemporal as well as energetic heterogeneities therein. This presentation will exemplify the efficacy of single-emitter spectroscopy to elucidate energetic inhomogeneity in two categories of luminescent semiconductor nanocrystals (undoped and dopedquantum-dots). Further, I will discuss the utility of single-molecule translational and rotational mobility measurements to provide insights on the extent of spatial and dynamic heterogeneity in polymer thin-films during plasticization, a process which involves solvent induced lowering of the glass transition temperature.

 

November 13, 2014 at 11.30 am in AG-66

Title :

Synthesis, Characterization and Applications of Mixed Metal Oxide Nanoparticles

Abstract :

Metal oxide nanoparticles play a very important role in various fields as they exhibit interesting optical, electronic and magnetic properties. Moreover the combination of two or more metal oxides can lead to materials with multi-functional properties. Aim of my research work was to control of size, shape and homogeneity for mixed metal oxide nanoparticles, studies on their optical and magnetic properties and explore some possible applications. During my doctorate research, I have synthesized core-shell nanoparticles CuO@NiO and SiO2@NiO core-shell nanoparticles by homogeneous precipitation method, binary mixed metal oxide nanoparticles SnO2-MgO, TiO2-MgO, NiO-ZnO, NiO-CuO and NiO-MgO and aluminate nanoparticles (CoAl2O4, NiAl2O4 and CuAl2O4) by sol-gel method. The synthesized nanoparticles have been characterized using different analytical techniques as XRD, TGA, CHN analysis, FT-IR, FE-SEM, EDXA, TEM, SAED, surface area analyser, UV-Vis DRS and SQUID. Some possible applications have also been explored such as catalytic reduction of 4-nitrophenol (4-NP), photocatalytic degradation of methylene blue (MB), adsorption of MB, and destructive adsorption of paraoxon. The CuO@NiO core-shell nanoparticles show better efficiency in the reduction of 4-NP compared to that of pure NiO and CuO nanoparticles. The NiO@SiO2 core-shell nanoparticles act as better adsorbent for MB compared to pure NiO nanoparticles and silica spheres. The SnO2-MgO nanoparticles act as an efficient photocatalyst towards the photodegradation of MB. The reactivity of the metal aluminate nanoparticles was investigated using the destructive adsorption of paraoxon and catalytic reduction of p-nitrophenol.

November 11, 2014 at 2.30 pm in AG-69

Title : 

Computational Understanding on Structural and Bonding Aspects of Molecules and Enzymes

Abstract :

Atomic and electronic structure is the origin of all the chemical and physical properties of chemical matter. Knowing the structure of molecules is extremely helpful to interpretthe experimental outcomes of various structural characterizations, reactivity and as well improves and predicts the properties of novel materials. Depicting the bonding aspects of the chemical matter is the holy grail of structural chemistry.

In this perspective, I will illustrate the insights that have emerged from theoretical studies on borodiphospholes and phosphodiesterase enzyme.In borodiphospholes, we found a structural diversity in various isolobalcyclopentadienyl ligands and through molecular orbital studies we depict the bonding aspects and origin for different stability of structures. Interestingly, in phosphodiesteraseenzymes we unravel the origin for secondary structural changes in the protein and how the structure is influential withcrystalline pH conditions and further implications in designing inhibitors. I finally discuss the strategic plan to model spectroscopic properties of the metalloenzymes and a few challenging enzymatic oxidation reactions that shall open up new vistas in understanding these enzymes.

 

November 10, 2014 at 4.00 pm in AG-69

Title :

QMMM Approach for Elucidating the Reaction Mechanisms of Heme and Nonheme Enzymes

Abstract :

Warshel and Levitt’sidea of quantum mechanical/molecular mechanical (QM/MM)approach has opened the door to model complex chemical systems such as enzymes and probe their reaction mechanisms. This approach combines a QM level of theory to describe the site where chemical reactions or electronic excitations occur and classical force field MM level to capture effects of the environment. In the recent times, state-of-the-art in QM/MM method gained immense importance as it provided high-accurate barriers, atomistic-level insights on mechanistic proposals, spectroscopic properties, and effects of mutations on reactivity of enzymes.

In the present talk I will focus on the highlights of the approach and the insights obtained recently in understanding the insilico mutation of F429H of heme (CYP 2B4) enzyme and reveal a novelDNA repair mechanism by AlkB a nonheme enzyme. Besides, I will discuss briefly my future interest in using this approach to understand the fundamental process in biological catalysts of oxidative enzymes that have broad academic and industrial applications.

November 3, 2014 at 2.30 pm in NMR Conference Room

Title :

Allostery in Chaperonins : Mechanism and Function

October 28, 2014 at 2.30 pm in AG-69

Title :

Probing the atomic-level structure of nanomaterials and nanocatalysts and using solid-state NMR enhanced by Dynamic Nuclear Polarization

Abstract :

Nanostructured materials, including micro- or meso-porous solids as well as nanoparticles, are promising systems for many important applications, including catalysis, gas storage, drug delivery, medical imaging and the capture of radioactive compounds. The rational design of these nanostructured materials requires a clear understanding of structure–property relationships and hence calls for characterization methods endowed with atomic resolution. As a local and non-destructive technique, solid-state nuclear magnetic resonance (NMR) provides precious insight into the atomic-scale structure and dynamics of nanomaterials. Nevertheless, the low sensitivity of NMR often precludes the observation of surface species or defects, particularly when the observed nuclei have low gyromagnetic ratios, low natural abundances or long longitudinal relaxation times (T1).

In this context, we have recently demonstrated that Dynamic Nuclear Polarization (DNP) can enhance the sensitivity of solid-state NMR experiments and hence provides new insights into the functional properties of nanostructured materials, including mesoporous silica1,2, mesoporous alumina3, microporous metal-organic frameworks4 and nanoparticles.5 Sensitivity enhancements of 1-2 orders of magnitude compared to conventional NMR has enabled an easy detection of surface and defect sites.

DNP-NMR is notably a powerful tool to probe the grafting mode of organic moieties on silica surface.2 More recently we have shown in collaboration with V. Polshettiwar from TIFR that DNP-NMR provides crucial insights to understand the catalytic activity of nitridated fibrous silica nanoparticles. We have also used the high sensitivity of DNP-NMR to probe proximities between Al sites near the surface of mesoporous alumina.3

 References

  1. O. Lafon, M. Rosay, F. Aussenac, X. Lu, J. Trébosc, O. Cristini, C. Kinowski, N. Touati, H. Vezin, J.-P. Amoureux, Angew. Chem. Int. Ed. 50 (2011) 8367.
  2. O. Lafon, A. S. Lilly Thankamony, T. Kobayashi, D. Carnevale, V. Vitzthum, I. I. Slowing, K. Kandel, H. Vezin, J.-P. Amoureux, G. Bodenhausen, M. Pruski., J. Phys. Chem. C 117 (2013) 1375.
  3. D. Lee, H. Takahashi, A. S. Lilly Thankamony, J. P. Dacquin, M. Bardet, O. Lafon and G. De Paepe, J. Am. Chem. Soc. 134 (2012) 18491.
  4. F. Pourpoint, A. S. Lilly Thankamony, C. Volkringer, T. Loiseau, J. Trebosc, F. Aussenac, D. Carnevale, G. Bodenhausen, H. Vezin, O. Lafon, J.-P. Amoureux Chem. Commun. 50 (2014) 933.
  5. O. Lafon, A. S. Lilly Thankamony, M. Rosay, F. Aussenac, X. Lu, J. Trébosc, V. Bout-Roumazeilles, H. Vezin, J.-P. Amoureux, Chem. Commun. 49 (2013) 2864.

 

October 28, 2014 at 11.30 am in AG-80

Title :

Smart Polymer Coating: Deigning of Anti-wetting Surfaces & Developing Stable Liquid Crystal Based Chemical Sensor

Abstract :

Nature remains inspiration behind various interesting findings in literature and one of them is anti-wetting property that noticed in several living objects such as lotus leaves, rice leaves, butterfly wings, water strider legs etc. provides a platform to design materials for wide range of practical applications. Extremely water repelling surfaces in air called as superhydrophobic surfaces are one of the most recognized and well-studied anti-wetting material in literature. Intense efforts have been directed toward the design of synthetic mimics of these materials for the design of self-cleaning surfaces, coatings that prevent corrosion or fogging, and advanced materials for water harvesting, oil-water separation, and a host of other emerging applications. A common approach to the design of synthetic superhydrophobic surfaces is one inspired by the natural structure of the lotus leaf, and generally involves the fabrication of surfaces with (i) appropriate combinations of microscale and nanoscale topography topped by (ii) a thin, low surface energy coating. While this approach is both useful and widely practiced, the practical utility of materials having this design is reduced in scenarios that expose them to physical insults (e.g., scratches) that can compromise low-energy coatings or physically degrade, remove, or destroy micro- and nanoscale surfaces features required to repel water and maintain non-wetting behavior. The pursuit of superhydrophobic surfaces that are physically robust and mechanically durable is a vibrant area of research and is important in both fundamental and applied contexts. Here, in my talk I will talk about how to design a robust and self-healing superhydrophobic coating based on three dimensional porous polymer coating and their several prospective applications such as drug delivery, guided water transfer etc. In second part of my presentation, I will talk about thermotropic liquid crystal droplets in context of sensing amphiphilic molecules. Liquid crystal droplet has immense prospect in sensing application-but at the same time, they are extremely sensitive, and they lose their property even after interacting with bare glass surface. Very Briefly, I will talk about how to decorating the thermotropic liquid crystal droplets with polymer assembly so that I can easily attach them on surface of various objects without disrupting their property.

October 27, 2014 at 4.00 pm in AG-69

Title :

Anti-Fouling Slippery Surface: An Approach to Design Advanced Materials

Abstract :

Fabrication of robust synthetic materials with antifouling properties would have broad technological implications for areas ranging from biomedical devices to fuel transport to architecture but has proven to be extremely challenging. Natural inspired non-wetting structures, particularly, Slippery Lubricant-Infused Porous Surfaces (SLIPS) that outperform state-of-the-art synthetic surfaces in their ability to resist ice and microbial adhesion and repel various simple and complex liquids. By coordinating surface nanostructuring, chemical functionalization and lubricant properties, one can design stable, shear-tolerant liquid-repellent coatings and manufacture them on arbitrary materials and complex shapes. The slippery surfaces can find important applications in fluid handling and transportation, small molecule sensing, and as antifouling surfaces against highly contaminating media operating in extreme environments. I will talk about how to design a polymer based universal SLIPS coating on various substrate that are with arbitrary shape and size. I will also give brief overview of some fundamental aspects which controls the adhesive behavior of this property that can be useful in microfluidics application. Aspects of controlled & guided transfer of small aqueous droplet based on SLIPS by applying rotational motion will be discussed and I will also talk about selective transfer and transport of liquid using hydrophilic-SLIPS patterned surface. It’s always hard to visualize directly with bare eyes a phenomena that is happening in nano scale, - but slippery surface (with proper designing) that is loaded with anisotropic lubricant allows events that occur at the nanoscale level to be observed at the spatial scale of the naked eye without the need for additional instrumentation. Finally, I will present its strong resistance towards fungal and bacterial attachment, thus eventually help to prevent biomass/biofilm formation.

October 20, 2014 at 4.00 pm in AG-69

Title :

Theoretical Studies on Size Selected Solvated Clusters: Understanding Towards Certain Macroscopic Properties

Abstract :

Small size molecular systems encapsulated in solvent clusters of different size are considered as model system for studying the influence of solvation on various fundamental molecular properties and processes. We will talk on structure, stability, vibrational and photoelectron spectroscopic properties of molecules in different size solvent clusters. We will discuss on a new general relation derived for size dependent detachment energy of negatively charged finite size clusters based on a microscopic theory and its performance to predict bulk detachment energy. We will also compare conformational averaged IR spectra of size selected hydrated clusters with measured spectra.

 

In macroscopic description, a strong acid means an acid that ionizes fully in aqueous solution whereas a weak acid does not ionize completely in such an environment. Thus, the ability to transfer a proton to a water molecule is the key to the characteristic feature of an acid. In the context of microscopic description of strength of an acid, one may ask a fundamental question: how many water molecules are required to ionize an acid molecule? In this talk, we plan to quest for answers of such queries based on a few case studies.

October 13, 2014 at 4.00 pm in AG-69

Title :

Accurate and Efficient Quantum Dynamics for Photo-Absorption and Molecule-Surface Scattering Processes

Abstract :

The major focus of the talk will be to explore the efficiency of parallelized TDDVR algorithm to perform dynamics on vibronically coupled electronic manifold for photo-absorption spectra [1] and molecule-surface scattering problem [2]. The parallelized algorithm shows closely linear scalability with increasing number of processors. The dynamical outcomes, e.g., population, photoelectron spectra and diffused interstellar bands etc. of this quantum-classical approach show good agreement with the findings of well established quantum dynamical MCTDH method [3]as well as experimental observations. We also carry out four (4D X 2D) and six (6D) dimensional quantum dynamics on an effective Hamiltonian derived by assuming weakly correlated interactions between molecular DOFs with surface modes and electron-hole pair (elhp) excitations through a Hartree product type wave function and depict the calculated sticking/transition probabilities as well as energy transfer from molecule to the surface at different surface temperature for D2(v=0, 1; j=0) - Cu(111) collision. The phonon modes change the chemisorption process, whereas both phonon and elhp interactions show physically meaningful trend both for sticking as well as transition probabilities w.r.t other theoretical calculations [4] and experimental results [5,6].


References:

  1. B. A. Khan, S. Sardar, T. Sahoo, P. Sarkar, S. Adhikari, J. Theor. Comp. Chem., 12, 1350042 (2013).
  2. S. Mandal, T. Sahoo, S. Ghosh, S. Adhikari, J. Phys. Chem A, (submitted, 2014).
  3. S. Ghanta, V. S. Reddy, S. Mahapatra, Phys. Chem. Chem. Phys., 13, 14523 (2011).
  4. J. C. Tremblay, G. Fuechsel, P. Saalfrank, Phy. Rev. B, 86, 045438 (2012).
  5. C. T. Rettner, D. J. Auerbach, A. H. Michelsen, Phy. Rev. Lett., 68, 1164 (1992).
  6. C. T. Rettner, A. H. Michelsen, D. J. Auerbach, Chem. Phys. 175, 157 (1993).

September 12, 2014 at 2.30 pm in AG-80

Title :

Structural Biochemistry : Insights into Biological Reactions

Abstract :

A combination of X-ray crystallographic and biochemical techniques can be employed to develop insights into several aspects of biological function like mechanism of catalysis, structure-function relationships, protein-protein interactions in enzymes and protein-DNA regulation. The three-dimensional structure enables one to visualize protein structures at the atomic level and enhances our understanding of protein function and combined with other tools can facilitate understanding of the allosteric changes necessary for catalysis.

In this talk we discuss two enzyme systems: the first problem deals with deciphering the structure-activity and evolutionary relationships of enzymes involved in nucleobase
deamination. The enzyme under investigation, NE0047 was established to be a guanine deaminase with moonlighting activity towards ammeline. Subsequently, the allosteric mechanism of action and structural basis of substrate specificity was determined. By utilizing the information obtained, the enzyme was further engineered so that it can function either exclusively as a guanine deaminase or serve as a specific ammeline deaminase with no cross reactivity.

The second work deals with understanding the mechanism of antibiotic regulation and
resistance in Streptomyces. Streptomyces species contribute to two-third of the naturally occurring antibiotics. Production of antibiotics and resistance pathways in these species are dictated by interplay of transcriptional regulatory proteins. These proteins belong to the tetracycline family of efflux pump regulators and possess a ligand binding and a DNA binding site, both of which remain elusive. To decipher the structural mechanism of action, here we present the crystal structure of CprB (a putative regulator) in complex with its consensus DNA element. The binding of the DNA induces the restructuring of the CprB dimeric interface, thereby inducing a pendulum like motion. This facilitates transcription regulation via conformationally switching of the protein to the repressed form. Furthermore, it was established that CprB is a pleotropic regulator that also autoregulates it own expression. The identity of the ligand that induces transcriptional activation of CprB was additionally explored and it was concluded that CprB likely possess dual triggers. It may be induced by quorum sensing molecules in early stages of growth and antibiotic intermediates in late growth phase.