Molecular Simulation of Long Time Structural Evolution in Nanomaterials
Materials used in energy applications, often undergo structural transformation that are crucial to the operation of the device. We have looked at three different materials to understand various aspects of their structural evolution at long time scale. These materials include i) Si used as an anode in lithium ion battery, ii) nanoporous metal alloys used as catalysts and iii) metal nanoparticles which is again used in catalysis. During lithiation/delithiation process, an amorphous lithiated phase is formed which is separated from the pure Si phase with a sharp phase boundary. The entire lithiation/delithiation process majorly depends on the migration of this phase boundary. When any lithiation occurs, due to presence of Li atoms in the system, we observe certain amount strain evolved. We have studied the effect of strain on the lithium diffusion barrier in bulk Si using nudged-elastic band (NEB) method applying modified embedded atom method (MEAM) as interatomic potential. Nanoporous material is usually obtained by dealloying method where electrochemically active species undergoes dissolution process whereas electrochemically noble material agglomerates and forms new cluster of islands resulting in formation of several ligaments and nodes. To understand the structural morphology of these nanoporous materials, we need a characterization tool which can quantify them correctly. So we have developed a characterization technique to calculate the size (length/diameter/area) distribution of nanoporous ligaments and facets using of connectivity lists for sites. Understanding the behavior of different response surface like extent of dissolution, surface area of various facet planes with perturbation of different operating conditions like temperature, binding energy, composition or dissolution pre-factor is also important because this will help to provide an insight about the morphological evolution of different nanoporous structure and importance of parameters in dealloying process. A response surface model analysis for different dealloying times varying with different important controllable parameters is performed to understand the insight how different responses change with a small perturbation in any of the controllable parameters. Both of these systems are very complicated. Understanding the detailed kinetics of these systems is not straight forward. Novel simulation techniques are required which can systematically determine the relevant pathways required to understand the kinetic mechanism of the complete system. We have developed a MD based KMC simulation technique to determine the relevant pathways systematically. We have applied our framework on an Ag cluster system to understand the detail mechanism of relevant pathways.
A tale of two proteins: What folding dynamics can tell us about the function of structurally similar proteins
Protein sequences have been optimized by evolution to facilitate fast folding (folding on a biologically relevant timescale). This implies that residues selected for folding are less likely to participate in non-native stabilizing interactions. Such interactions need to be broken before native interactions are formed and this breaking and forming slows folding. Functional residues, on the other hand, have been selected for function, may not be optimal for folding, may facilitate the formation of non-native traps and slow folding. My group has been working on understanding the effect of such non-optimal functional residues on folding energy landscapes using computational models.
In this talk, I will present results on the folding of two structurally similar but functionally distinct proteins: monellin (a sweet protein) and stefin-B (a cysteine protease inhibitor). Despite having similar structures, we find that their sequences and in turn, the energetics of the two proteins are tuned to facilitate their differing functions and these energetic differences lead to entirely different folding characteristics. Understanding these differences computationally has led to diverse predictions which could drive the design of intrinsically disordered proteins that fold upon binding as well as protein assembly. I will also outline some experiments that support these results.
Coordination Chemistry of Cyclic Peptides: Possible Biological Functions of the Patellamides
Cyclic pseudo-peptides, derived from marine metabolites of the genus Lissoclinum bistratum and Lissoclinum patella have attracted scientific interest in the last two decades. Their structural properties and solution dynamics were analyzed in detail, elaborate synthetic procedures for the natural products and synthetic derivatives were developed, the biosynthetic pathways were studied and it now is possible to produce them biosynthetically. A major focus in the last decade was on their CuII – more recently also on the ZnII – coordination chemistry, as a number of studies have indicated that di-nuclear CuII and ZnII complexes of cyclic peptides may be involved in the ascidians’ metabolism. Recent in vitro studies indicate that the dicopper(II) complexes have phosphatase, carbonic anhydrase, lactamase and glycosidase activity. Intererstingly, first in vivo studies with a patellamide derivative with an appended fluorescence molecule indicate that CuII is coordinated to the patellamides in the prochloron cells.
Nonribosomal Polyamides Binder Discovery of Ebola Glycoprotein
Development of a Platform for Peptidomimetic Covalent Binder Discovery
Specific recognition of biomolecules in the complex biological milieu inspires principally every aspect of biology and has been a long-standing goal of biological and medicinal chemists. On that front, nonribosomal amino acids and peptidomimetics have revealed great potential through the discovery of potent inhibitors. Designing novel molecular scaffolds that allow specific biomolecule recognition requires broad expertise and understanding in the area of organic synthesis, chemical biology, molecular design, and high-throughput screening technology. Since 2008, I have focused my efforts on discovering novel chemical entities containing amino acids that enable the recognition of biomolecules of interest. Here, I present strategies of molecular recognition via noncovalent and covalent interactions.
In the second day presentation, I will describe noncovalent recognition in finding a binder of Ebola glycoprotein utilizing high-throughput screening of large peptide libraries. I prepared large combinatorial libraries comprising millions of peptides featuring nonribosomal amino acids and discovered the first peptide based binder of Ebola glycoprotein.
In the future, I aim at developing an innovative approach for the discovery of peptidomimetic therapeutics and diagnostics for the treatment of neglected tropical diseases. My long term vision is to develop dengue inhibitors by specifically targeting dengue envelope protein. I believe, the discovery of such chemical entities will have a tremendous beneficial impact on Indian society and tropical countries in general.
Application of Iminoboronate in Chemistry and Biology
In past decades, dynamic covalent chemistry has shown its great potential in the area of combinatorial chemistry and molecular recognition. Nonetheless, in this area, a few reactions have been explored that can allow selective recognition of endogenous nucleophile in reversible manner at physiological pH. Iminoboronate chemistry is one of them, which allow to capture amine at neutral pH. Here, I will present, how the fundamental understanding of iminoboronate complex formation was leveraged for numerous biological applications. Iminoboronate chemistry was known, however, it was poorly understood. For the first time, my work has revealed the dynamic nature of iminoboronate formation at physiological conditions.
In this talk, I will focus first on the dynamic covalent recognition of biologically important molecules via iminoboronate chemistry. Using this unique chemistry, I developed strategies for the specific recognition of gram-positive bacteria in blood serum . Importantly, this approach has the potential to transform the way bacterial infection diagnostics are performed in clinical setting. Harnessing the power of this iminoboronate formation, I also developed a new and efficient synthetic access for modular cyclic peptides  along with an unprecedented bioorthogonal reaction . For instance, the impact of these findings were illustrated by a new bioorthogonal labeling technology to detect gramnegative bacteria selectively. To take the kinetic advantage of iminoboronate formation, a strategy of fast and selective conjugation of N-terminal cysteine containing protein will be demonstrated .
1.Targeting Bacteria via Iminoboronate Chemistry of Amine-Presenting Lipids. Bandyopadhyay, A., MaCarthy, K., Kelly, M., Gao, J. Nat. Commun., 2015, 6:6561.
2.Iminoboronate-based peptide cyclization that responds to pH, oxidation, and small molecule modulators. Bandyopadhyay, A., Gao, J.; J. Am. Chem. Soc., 2016, 138, 2098.
3.Fast Diazaborine Formation of Semicarbazide Enables Facile Labeling of Bacterial Pathogens. Bandyopadhyay, A., Cambray, S., Gao, J.; J. Am. Chem. Soc., 2017, 139, 871.
4.Fast and selective labeling of N-terminal cysteines at neutral pH via thiazolidino boronate formation. Bandyopadhyay, A., Cambray, S., Gao, J. Chem. Sci., 2016, 7, 4589.
Bio-nanoconjugation of Mutant Cytochrome P450cam (CYP101) for electro-biocatalysis
Dipole Organization and Membrane Biophysics: A Tale of Two Studies
Biological membranes are complex assemblies of lipids and proteins that allow cellular compartmentalization and act as an interface, through which cells communicate with each other and with the external milieu. In physical terms, membranes can be treated as a complex oriented fluid which is a weakly coupled, non-covalent, and anisotropic assembly of molecules in two-dimensions, and can therefore be treated as soft matter.
In this lecture, I will focus on the application of red edge excitation shift (REES) and membrane dipole potential to explore organization and dynamics of membrane lipids and proteins. Both these phenomena are dependent on organization of membrane dipoles.
1.Haldar, S., Chaudhuri, A., and Chattopadhyay, A. (2011) J. Phys. Chem. B 115: 5693-5706 (Feature Article).
2.Chattopadhyay, A., and Haldar, S. (2014) “Dynamic Insight into Protein Structure utilizing Red Edge Excitation Shift” Acc. Chem. Res. 47: 12-19.
3. Haldar, S., Kanaparthi, R.K., Samanta, A., and Chattopadhyay, A. (2012) Biophys. J. 102: 1561-1569.
4.Lajevardipour, A., Chon, J.W.M., Chattopadhyay, A., and Clayton, A.H.A. (2016) Sci. Rep. 6: 37038.
5.Sarkar, P., Chakraborty, H., and Chattopadhyay, A. (2017) Sci. Rep. 7: 4484.
Physico-chemical Aspects of Synthesis, Characterization of Nanostructured Materials and its Biological Applications
Nanoparticles are promising candidate in interdisciplinary research in the field of physics, chemistry and biology. This talk includes synthesis of different type of nanomaterials (core and core shell quantum dots, silver nanoparticle, graphene, nanowire) and nano-bio conjugate with some interesting features and also thermodynamics involved in the formation of nanohybrids. Synthesis in aqueous route is preferred in order to allow the nanoparticles well-suited for biological applications. However, organic synthesis leads to better quality nanoparticles. Surface functionalization of organic nanoparticles with different organic ligands and biomolecules is another way to make them water soluble as well as biocompatible. Next, interaction of some important biological molecules, e.g. enzyme, peptide, vitamin etc. with the as synthesized quantum dot nanoparticles will be described, and a simple strategy for sensing those biomolecules have been proposed based on the fluorescence based interaction between quantum dot nanoparticles and biomolecules. Further designing quantum dot nanoparticle based multichannel biosensor will be discussed for sensing human serum proteins. Next, enhancing enzyme activity through incorporating nanoparticles into enzyme, i.e. designing nanozyme will be discussed.
The role of conformational dynamics in molecular recognition
Conformational dynamics plays a fundamental role in molecular recognition and activity in proteins. Ubiquitin and ubiquitin-like proteins are involved in nearly all aspects of cellular function. Nuclear magnetic resonance (NMR) spectroscopy and Molecular dynamics simulations were used to show that conformational selection underlies the allosteric interaction between ubiquitin conjugating enzyme (E2) and ubiquitin ligase (E3) . The E2, Ube2g2 functions with the canonical E3, gp78 to assemble poly-ubiquitin chains on target substrates. Two domains of the gp78, RING and G2BR, bind to two distinct regions of Ube2g2, and activate it for ubiquitin (Ub) transfer. The conformational dynamics in Ube2g2 reveals a clear correlation of binding G2BR and RING with sequential progression towards Ub transfer. The interrelationship of the existence and exchange between ground and excited states leads to a dynamic energy landscape model, in which the redistribution of populations contributes to allostery and activation . Briefly, our current results about conformational selection of Ubiquitin will be discussed. Subsequently, I will discuss systems where the functional implications of conformational selection mechanism will be explored. The divergent evolution of proteins has been hypothesized to rely on the conformational selection mechanism . The Small Ubiquitin-like Modifier (SUMO) protein can be investigated as a model system to test the hypothesis that conformational selection is a relic of evolution in ubiquitin-like protein family . The conformational selection in a transporter protein partitioning between aqueous and lipid phases remains unexplored. I will discuss the selection of different conformations of the Synaptotagmin-like mitochondrial-lipid binding proteins (SMP) domain of the transporter protein Extended synaptotagmin (Esyt)  based on the physico-chemical properties (e.g., hydrophobicity) by different phases (aqueous, lipid) existing within the neuron, which is involved in transfer of lipid molecules from endoplasmic reticulum to plasma membrane in the axons . The mechanism of Esyt has importance in understanding the axon degeneration in genetic diseases hereditary spastic paraplegia (HSP)  and amyotrophic lateral sclerosis (ALS) .
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Conformational selection in a protein-protein interaction
Molecular recognition plays a central role in biology and protein dynamics has been acknowledged to be important in this process. However, it has been intensely debated for the last 50 years whether conformational changes happen before ligand binding to produce a binding-competent state (conformational selection) or are caused in response to ligand binding (induced fit) . Proposals for both mechanisms in protein-protein interaction have been primarily based on structural arguments. However, the distinction between them is a question of the probabilities of going via these two opposing pathways. In this seminar I will discuss a direct demonstration of exclusive conformational selection in protein-protein recognition by measuring the flux for rhodopsin kinase binding to its regulator recoverin, an important molecular recognition in the vision system . The combined use of nuclear magnetic resonance (NMR) spectroscopy, stopped-flow kinetics and isothermal calorimetry establishes that protein dynamics in free recoverin limits the overall rate of binding.
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2. Chakrabarti et al. (2016) Cell Rep. 14 32-42.
Integrity During Crisis in Colloidal Droplets
Colloids are ubiquitous and it forms an interesting branch of soft matter science owing to the nature of interactions among the constituent phases. Such interactions are amalgamation of various effects, namely, electro-static, van der Waal, excluded volume, etc. As soon as the continuous medium of a colloidal dispersion i.e., the solvent, starts disappearing, as by evaporation, the interaction among the particles gets altered. The extent of modification depends on the competitive dominance of the aforementioned factors. In fact, the phenomenon of evaporation of suspension droplets is widely used in various industries including food and pharmaceutical industries and this process is known as spray drying. Fast evaporating droplets exhibit spectacular behavior due to sudden transition from liquid to powder state associated with assembly of the nanostructures as drive by evaporation. Since last decade, the above mentioned spray drying process has re-embellished itself in nano-science and nano-technology. Using such evaporative technique, we have synthesized various hierarchically structured micro/meso/macro-porous granules. We have demonstrated sphere to doughnut like shape transformation during spray drying and quantified the role of various physicochemical factors responsible for effecting such transformation through buckling. Potential application of such spray dried micro-granules in filtration and bioremediation has also been indicated. Understanding the mesoscopic structure and correlation among the constituent nanostructures in a granule is crucial. In this regard, small-angle neutron scattering (SANS), X-ray scattering (SAXS) and scanning electron microscopy (SEM) have been found effective tools in probing such nano-structured granules. In this presentation, we will discuss some of our recent results on such spray dried micro-granules and will touch upon a few potential applications of such porous granules.
Designing Azurin Mutants Polygene to get Deeper Insights into Mechanical Properties of Azurin
Modulation of emission signaling pathway through allosteric control on the conformational rigidity of coumarin-imidazole conjugate
The allosteric regulation in the biological system is controlled at the molecular level by recognition events that are triggered by subtle conformational changes of the proteins.1 Although it is very challenging to mimic such complex communication pathways, one can still be inspired by these systems and design prototype that can give into fundamentals of molecular recognition2 in physiological environments. There seems to be a significant lag in the area of chemically controlled conformational switches that modulate new fluorescence signaling pathway through allostery; bridging this gap may lead to novel molecular systems. The design of such molecular systems represents a promising avenue for finding and manipulating allosteric networks3 in the biology.
In this presentation, I will discuss about a prototype based on coumarin-imidazole conjugate which undergo conformational changes through distal intramolecular H-bonding interactions.4 The key factor behind this conformational switching is a cooperative effect that involves coumarin side arm, solvents, and leads to a conformational or dynamic changes in the distal coumarin sidearm through intramolecular H-bonds, affecting its emission output function. So we hypothesized that the combination of distal intramolecular H-bond interactions and allostery results in the observed effects on the fluorescence output signaling pathway. The concept of new emission signaling pathways caused by conformational switching between two states offers a new paradigm to introduce functional allostery in macromolecular backbones.
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4. Bhattacharjee, I.; Ghosh, N.; Raina, A.; Dasgupta, J.; Ray, D.- Manuscript under communication
Tessellation Models for Microstructure Evolution
Accurate morphological representation of polycrystalline microstructures is the key to structure-property linkage. Spatial tessellations exhibit great resemblance with the real microstructure evolution, which are driven by nucleation and growth. Voronoi, Avarami and Laguerre tessellations are the most popular models among the spatial tessellation models, but are only a small subset of the wide spectrum of the real microstructure evolution. Specifically, none of these models capture the anisotropy of grain shapes. The current research work proposes generalized ellipsoidal growth, in which grains grow as ellipsoids with specified 3D orientation and with velocities as a function of their size and initiate at different times from random nucleation sites represented by a spatial point process. This can be represented by a marked point process random field model. The mathematical representation of the grain cells, thus formed, is developed. This could be extended to the non-trivial inverse problem of locating a grain nucleation site from the grain centroid and volume data. This is demonstrated on data generated using diffraction Contrast Tomography (DCT).
Designing Carbon-Metal Oxide Nanostructures for Energy Applications
The ever increasing world energy needs, the severity of environmental pollution issues, limited fossil fuel resources, have triggered extensive research in pursuit of efficient renewable energy sources and sustainable storage technologies. Electrochemical capacitors (ECs) often called supercapacitors (SCs) are promising clean energy storage solutions for high power management and grid applications. In general, the ultimate performance characteristics of SCs primarily depend on the way constituent electrode materials are engineered and how the electrodes are fabricated. The presentation is aimed at exploring three important aspects of the SC, such as i) simple, continuous and energy-efficient method to synthesize high-quality carbon nanomaterials such as hydrophilic carbon nano-onions (CNOs), ii) enhancing performance of such nanocarbon by various nanocomposites and efficient heteroatoms doping techniques, iii) working on different SC configurations (symmetric & asymmetric) to enhance the specific energy and power density of the device and iv) to evaluate the device performance by using industrially recommended best practices and methods to get reliable performance data using fabricated devices which actually mimic the real supercapacitor in market. The carried out PhD research work essentially establishes an inherent relationship among synthesis-structure-property-application of as-synthesized CNOs, its nanocomposites and doped CNOs at the nanoscale.