From Molecular to Supported Single Atom Catalysts: Catalysis in Homogeneous and Heterogeneous Phase
Polyoxometalates (POMs) are best known for their acidic properties, ability towards electron transfer (ET), proton transfer (PT), proton coupled electron transfer (PCET) and electron transfer-oxygen transfer (ET-OT) reactions. These abilities strictly depend on addenda atoms incorporated to the POM. For example, phosphovanadomolybdic acid, H5PV2Mo10O40 can act as ET-OT agent for the oxidation of anthracene to anthraquinone whereas H5PMo12O40 can act as only ET agent. Moreover, reaction medium plays a decisive role in the rate of the reaction. Using a mixture of water and sulfuric acid as solvent, we were able to protonate H5PV2Mo12O40, which facilitates the ET-OT reactions for the activation of C-H bond of toluene and benzene., Electron paramagnetic resonance (EPR) spectroscopy was used to detect the presence of organic radical in the X-band.
In a different study, cavity of polyoxometalate wheel such as Mo132 was used as a nano-reactor which allows selective organic molecules to assemble inside the POM and further halogen migration reaction and Friedel-Craft arylation reaction was observed due to intrinsic acidity generated inside the cavity. Two-dimensional NMR, such as rotating frame overhause effect spectroscopy (ROESY) and heteronuclear overhause effect spectroscopy (HOESY) were used to understand the interactions between the organic molecules and the POMs.
All these results lead to remarkably interesting questions such as (a) can we mimic these reactions in heterogeneous phase? (b) can we anchor single atoms over support and understand the behavior of molecular catalysts? (c) can we tune the surrounding environment of the metal via different metal-support interaction? Synchrotron based X-ray absorption spectroscopy will be used as one of the major characterization tools in order to derive coordination number, oxidation state and symmetry of the supported single atom.
 A. M. Khenkin, L. Weiner, Y. Wang and R. Neumann; J. Am. Chem. Soc. 2001, 123, 35, 8531–8542
B. B. Sarma, R. Neumann; Nature Communications, 5, 4621, 2014
B. B. Sarma, I. Efremenko, R. Neumann; J. Am. Chem. Soc., 2015, 137, 18, 5916–5922
 B. B. Sarma, R. Carmieli, A. Collauto, I. Efremenko, J. M. L. Martin, R. Neumann; ACS Catalysis, 2016, 6, 6403-6407
 B. B. Sarma, L. Avram-Biton and R. Neumann; Chem. Eur. J., 2016, 22, 43, 15231 – 15236.
Chemical Tools for Tracking Phospholipid Dynamics
Improving Device Performance of PbS Quantum Dot Solar Cells Using Inorganic Hole Transport Layers
Colloidal quantum dots (CQDs) are nanometer-scale semiconductor crystals. These "quantum dot" materials exhibiting three dimensional (3-D) confinement, are highly desired for their size-tunable optical properties synthesis routes utilizing organo-metallic precursors enable the production of nanocrystalline particles with nearly monodisperse size dispersions. I improved the efficiency of the colloidal PbS quantum dot solar cell efficiency by varying the device structure with the help of an inorganic hole transport materials like 2D-MoS2 nanosheets and by changing the chemical nature of the QD surface by ultraviolet ozone treatment (UVO). UVO treatment for few seconds lowers the Fermi energy level and increases p-doping through control oxidation of the PbS QD surface. I developed a two-stage solution-phase ligand exchange process by substitution of the organic counter cation with the inorganic metal cation is achieving superior stability and performance of the CsI and NaI treated PbS quantum dot solar cells.
Strain and support effects for enhanced electrocatalytic performance
The renewable energy resources have got a huge attention in lieu of fossil fuel-based energy resources due to the rise in environmental pollution along with a concomitant increase in global energy demand. The most challenging issue lies on the intermittent nature of these renewable resources. One of the important alternatives of these is use of fuel cells which uses chemical energy of a fuel and cleanly produces electricity without combustion. Electrocatalysis, used as the electrode material, accelerates the rate of an electrochemical reaction under a given electrical potential. The main aim in the development of an electrocatalyst is that the material designed should have better catalytic activities at a fairly cheaper cost. In a bi/multi-metallic system, with distinct lattice constants, a synergistic interaction modifies the electronic features such as position of d-band center and shift in core level with respect to the Fermi level and tunes the catalytic properties to be better than that of the individual metal analogues. The geometric (strain) and support effects in nanomaterials were studied for hydrogen evolution reaction (HER) and carbon dioxide (CO2) reduction. In this seminar, I will present the following research investigations:
The effect of surface strain in the carbon supported Pt3Co dealloyed catalyst towards HER has been studied. Dealloying process was adopted to generate the geometric strain in Pt3Co/C alloy by preferential dissolution of non-noble metal (Co) from the alloy and the improved activity in Pt3Co/C dealloy was due to the compressive strain generated in it.
The electrochemical reduction of carbon dioxide to recycle CO2 into CO (an important raw material of syn gas for the synthesis of industrially valuable products via Fischer–Tropsch process) was studied. Au NPs supported on RGO have been studied for CO2 reduction. The presence of defect sites on RGO in RGOAu, the influence of reducing agent (NaBH4) and the optimum concentration of Au on RGO support were studied for carbon dioxide reduction.
Understanding Protein-Protein Interaction in CDK1/Cyclin B and SARS-COV-2-RBD/ACE2 protein complex
In many diseases, protein-protein interactions (PPIs) in the functional protein complexes are found to be dysregulated, so understanding PPI and their regulation will help in designing the drug molecules to tackle these PPIs and hence disease. Here we have studied the PPI in two protein complexes, CDK1/cyclin B and SARS-COV-2-SPIKE/ACE2.
The protein-protein binding in CDK1-cyclin B which is an essential cell cycle regulator 1 is known to be a default process. Our molecular dynamics (MD) simulation result suggest that PPI between them is not a default process rather regulated by acetylation and ATP binding in CDK1. Based on this evidence, we propose the formation of the CDK1-cyclin B complex, first through deacetylation of CDK1 and then Cyclin B binding in presence of ATP.
The receptor-binding domain (RBD) in SPIKE protein from the SARS-COV-2 virus interacts with human cell receptor protein ACE2 and this interaction acts as an entry point for the virus into the human cell 2. The interaction of ACE2 with RBD is mainly dominated by a helix called SBP1 3 which opens a route for disrupting PPI between SPIKE and ACE2 through designing an inhibitor based on SBP1 peptide. However, it has been reported that removing the SBP1 helix from ACE2 disrupts the helicity of SBP1. So, to tackle this, we have applied a lactam group based linker on SBP1 and studied the linker position-dependent stability of SBP1. We found that stapling at specific positions in the SBP1 peptide drastically improved its helicity.
1-N. R. Brown, S. Korolchuk, M. P. Martin, W. A. Stanley, R. Moukhametzianov, M. E. Noble, and J. A. Endicott, “CDK1 structures reveal conserved and unique features of the essential cell cycle CDK ”, Nature Communications, vol. 6, pp. 1–12, 2015.
2-Renhong Yan, Yuanyuan Zhang, Yaning Li, Lu Xia, Yingying Guo, Qiang Zhou, “Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 ”, Science, vol. 367, pp. 1444-1448, 2020.
3-G. Zhang, S. Pomplun, A. R. Loftis, A. Loas, B. L. Pentelute “The first-in-class peptide binder to the SARS-CoV-2 spike protein’’ bioRxiv 2020.03.19.999318
Emotional Intelligence at the Workplace
Emotional intelligence, sometimes referred to as EQ ("emotional quotient"), refers to a person's ability to recognize, understand, manage, and reason with emotions. It is a critical ability when it comes to interpersonal communication—and a hot topic not only in psychology, but in the business world. The term was coined by psychologists in the 1990s.
Interest in emotion psychology and the concept of emotional intelligence really caught fire with the 1995 publication of Daniel Goleman's book "Emotional Intelligence: Why It Can Matter More Than IQ." In the book, Goleman argued that emotional intelligence was critical for predicting success in life. Emotional competencies, he argued, also played a particularly important role in the workplace. Researchers have suggested that emotional intelligence influences how well employees interact with their colleagues, and EQ is also thought to play a role in how workers manage stress and conflict. It also affects overall performance on the job. Other studies have linked emotional intelligence with job satisfaction. Studies have shown that employees with higher scores on measures of EQ also tend to be rated higher on measures of interpersonal functioning, leadership abilities, and stress management.
In the talk, the concept of EI will be introduced followed by a deliberation on how each one of us can improve this skill with training and practice, because if you want to succeed in the workplace and move up the career ladder, emotional intelligence is critical to your success.
I attended a workshop “Emotional Intelligence at the Workplace for Scientists/Technologies” organized by Centre for Organization Development, Hyderabad (Feb. 17-21, 2020), sponsored by Dept. of Science & Technology, Govt. of India, and the concepts of EI which I learnt in this are worth sharing with all colleagues.
Understanding the activation and regulation of the mitogen-activated protein kinase p38 using solution NMR spectroscopy
Enzymes, including kinases, require conformational and dynamic changes to perform their biological function. Conformational changes associated with the function are well-documented using X-ray crystallography and NMR spectroscopy. However, dynamic changes associated with allostery and catalysis are getting established. NMR spectroscopy is the method of choice for these studies as it reports directly on protein dynamics/motions across different time scales (ps to s; most of the catalytic activity occurs at this timescale).
Mitogen-activated protein kinases (MAPKs), including p38, belong to the family of ser/thr protein kinases that are essential for cell differentiation and autophagy. p38 becomes activated by phosphorylation of two residues (TxY) in its activation loop. Substrate binding occurs at a recognition sequence, commonly referred to as the D-motif or the Kinase Interaction Motif (KIM). Despite extensive efforts, the molecular mechanism of activation, including how p38 dynamics are correlated with activity and regulation, remains unclear. Here, the results of auto-correlated 15N fast (ns-ps) and intermediate timescale (s-ms) dynamics measurements to understand the activation and regulation of p38 will be presented. NMR relaxation measurements were performed on the different states along the activation pathway of p38, which includes phosphorylation, substrate, and ATP binding. Unexpectedly, our data showed that phosphorylation of p38 is important, but substrate binding is indeed key for the synchronization of the dynamics across the molecule to activate p38. And, it is this synchronization that allows for enhanced ATP recruitment and thus, the full activity of p38. Besides, the regulation of MAPKs is achieved via a plethora of regulatory proteins, including activating MAPKKs and an abundance of deactivating phosphatases. Although all regulatory proteins that include MAPK phosphatases, use identical interaction sites on MAPKs, they use distinct kinase interaction motif (KIM) sequences that are present in linear, peptide-like, or well-folded protein domains. To understand how the MAPK phosphatases, interact with substrates and elucidate the structural basis for the specificity of these regulatory proteins, we studied the interaction of the MAPK binding domain of a dual-specificity phosphatase (DUSP16) with p38, using integrated structural biology approaches the results of which, will also be presented.
Studies on Interaction of Peptides and Polymers with Phospholipid Bilayer
In this seminar, I’ll discuss my doctoral research on interaction of peptides and polymers with liposomes for drug delivery applications. Our work has technological potential in the area of drug delivery. But it can also serve as a model system for understanding how the membrane properties change due to interaction with drug delivery cargoes, drug molecules, peptides, and polymers.
Low endosomal escape efficiency of liposome following internalization into the endosomal compartment is one of the significant limitations to conventional liposomal drug delivery systems . The encapsulated drug in the liposome must reach into the cell cytoplasm through two membranes, one of the liposomes itself and other of the endosome, while avoiding degradation in the lysosomal environment. A possible solution for achieving endosomal escape and intracellular drug delivery is provided by pH sensitive cell-penetrating peptides. We have utilized a single giant unilamellar vesicle assay to study the kinetics of pH sensitive cell-penetrating peptide induced pore formation in vesicles. Moreover, kinetics of peptide induced leakage at single vesicle level, mechanism of pore formation in phospholipid bilayer, estimation of the rate constant of pore formation, and rate of increase in pore density as a function of peptide concentration addressed in our studies will also be discussed.
Rapid clearance of liposomes from the circulatory system is another major limitation associated with liposomes. Chitosan, a cationic linear polysaccharide has been widely used in polymer based liposomal drug delivery system because of its biodegradability, biocompatibility, non-toxicity, and mucoadhesive properties. In this study, chitosan-bearing giant unilamellar vesicles were prepared using inverse phase precursor method. We measured mechanical properties such as bending and area compressibility moduli and lysis tension using micropipette aspiration assay . Our findings demonstrate that incorporation of chitosan in phospholipid bilayers modulates the mechanical and transport properties of liposomes, which may affect their in vivo circulation time and drug release rate. Collectively, a deep understanding of the interaction of polymers and cell-penetrating peptides with phospholipid bilayer may help in designing an efficient liposomal drug delivery platform.
 T.M. Allen, P.R. Cullis, Liposomal drug delivery systems: From concept to clinical applications, Adv. Drug Deliv. Rev. 65 (2013) 36–48. doi:10.1016/j.addr.2012.09.037.
 H.P. James, S. Jadhav, Mechanical and transport properties of chitosan-zwitterionic phospholipid vesicles, Colloids Surfaces B Biointerfaces. 188 (2020) 110782.
Force Response and Unfolding Pathways of Ubiquitin using Steered Molecular Dynamics Simulations
Synthesis and Applications of Carbon Nano-onins and Carbon dots
The progress of nanotechnology, especially nano-materials based on carbon, has revamped the existing science and technology world. The carbon family has produced tremendous interest due to their varied potential applications since the discovery of fullerenes,1 followed by carbon nanotubes (CNTs),2 carbon nano-onions (CNOs),3 graphene,4 and, most recently, carbon dots.5 The synthesis and applications of fluorescent carbon nano-onions, carbon dots6 in the field of sensors and agriculture will be discussed in this talk. Carbon nano-onions were used as a growth promotor for gram plants.7 Entire life cycle stages of gram plants will be discussed. For the application of sensors, fluorescent carbon dots have been used. These carbon dots selectively detect trinitrophenol.8
1. Kroto, H. W.; Heath, J. R.; O’Brien, S. C.; Curl, R. F.; Smalley, R. E., C60: Buckminsterfullerene. Nature 1985, 318, (6042), 162-163.
2. Iijima, S., Helical microtubules of graphitic carbon. Nature 1991, 354, (6348), 56-58.
3. Ugarte, D., Curling and closure of graphitic networks under electron-beam irradiation. Nature 1992, 359, (6397), 707-709.
4. Novoselov, K. S.; Geim, A. K.; Morozov, S. V.; Jiang, D.; Zhang, Y.; Dubonos, S. V.; Grigorieva, I. V.; Firsov, A. A., Electric Field Effect in Atomically Thin Carbon Films. Science 2004, 306, (5696), 666.
5. Sun, Y.-P.; Zhou, B.; Lin, Y.; Wang, W.; Fernando, K. A. S.; Pathak, P.; Meziani, M. J.; Harruff, B. A.; Wang, X.; Wang, H.; Luo, P. G.; Yang, H.; Kose, M. E.; Chen, B.; Veca, L. M.; Xie, S.-Y., Quantum-Sized Carbon Dots for Bright and Colorful Photoluminescence. J. Am. Chem. Soc. 2006, 128, (24), 7756-7757.
6. Babar, D. G.; Sonkar, S. K.; Tripathi, K. M.; Sarkar, S., P2O5 Assisted Green Synthesis of Multicolor Fluorescent Water Soluble Carbon Dots. Journal of Nanoscience and Nanotechnology 2014, 14, (3), 2334-2342.
7. Sonkar, S. K.; Roy, M.; Babar, D. G.; Sarkar, S., Water soluble carbon nano-onions from wood wool as growth promoters for gram plants. Nanoscale 2012, 4, (24), 7670-7675.
8. Babar, D. G.; Garje, S. S., Nitrogen and Phosphorus Co-Doped Carbon Dots for Selective Detection of Nitro Explosives. ACS Omega 2020, 5, (6), 2710-2717.
Earth Abundant Metal Functionalized Graphene Based Hybrid Electrocatalyst for CO2 Reduction
Rapidly increasing CO2 in the atmosphere is becoming the big challenge of scientific community globally because of serious environmental and societal issues. The major contributor for CO2 is mostly from combustion of fossil fuel during industrialization. On the other end there is an increase in demand of energy because of globalization responsible for increase in level in atmosphere. It motivates to search for the ways to reduction of CO2 to other chemical intermediates and/or back to fuel. Among the existing conversion ways electrocatalytic approach by selecting appropriate cathode electrode nanomaterial is one of the most promising and cost effective approach to convert CO2 to variety of hydrocarbons. 
Further nanomaterials for electro catalysis are superior because of its compare to bulk large surface area, hence less utilization, spatial confinement, and many more. Another issue of it requires wide electrochemical window which controls the use of aqueous electrolytes. Depending up on electron transfer in electrochemistry of CO2 there are different types of product formed such as Hydrocarbons, alcohols, Formic acid etc.  In addition to this other structural issues of CO2 includes solubility, and comfortably of other reduced intermediates results into hamper its conversion. To overcome this barrier, we herewith used as-synthesized Graphene oxide decorated metal oxide hybrid electrocatalytic system for the reduction of CO2 considering their synergetic effect to useful product formic acid.  Moreover, as a one of the active component g-carbon nitrite (g-C3N4) is having highly polymeric class and consists of carbon and nitrogen with different types of allotropes with sheet-like structure, synthesized by simple way from commercially accessible and low-cost materials. Again, N-doping materials are having more active sites and a large number of defects because of Sp3 carbon atoms, which possess additional surface energy with enhanced electron enrichment for electrochemical activation of CO2 molecules. In the line of this we have synthesized non Nobel metal/metal oxide nanoparticles and decorated on graphene and g-carbon nitrite based hybrid electrocatalyst for electrochemical hydrogenation of CO2 to formate/formic acid. 
Furthermore reduction of formic acid to give methanol and finally methane as product which has widely used in petroleum industry as part of this formic acid important intermediate for came back again to fuel from CO2. Formic acid has natural antibacterial properties because of that used as antibacterial in food products as a preservative or on crops as a pesticide, production of leather, dyeing and finishing textiles, coagulant in many rubber manufacturing processes, it also helps tofermentation at a lower temperature,one of the basic raw materials of organic chemical and it has insect protective mechanisms. 
1. J. Qiao, Y. Liu, F. Hong, J. Zhang, A review of catalysts for the electroreduction of carbon dioxide to produce low-carbon fuels,Chem. Soc. Rev. 43 (2014) 631-675.
2. B. Khezri, A. C. Fisher, M. Pumera, CO2 reduction: the quest for electrocatalytic materials, J. Mater. Chem. A. 5 (2017) 8230-8246.
3. W. Zhang, Y. Hu, L. Ma, G. Zhu, Y. Wang, X. Xue, R. Chen, S. Yang, Z. Jin, Progress and Perspective of Electrocatalytic CO2 Reduction for Renewable Carbonaceous Fuels and Chemicals, Adv. Sci. 5 (2018) 1-25.
4. Q. Han, N. Chen, J. Zhanga, L. Qu, Graphene/graphitic carbon nitride hybrids for catalysis,
Mater. Horiz., 4 (2017) 832-850.
5. D. Du, R. Lan, J. Humphreys, Progress in inorganic cathode catalysts for electrochemical conversion of carbon dioxide into formate or formic acid, J. Appl. Electrochem. 47 (2017) 661-678.
Switching DNA Junction Binding ability of metallosupramolecular Nano-cylinder Helicates by rotaxination
In this talk I will be discussing a new class of rotaxane that is created by our research group at the University of Birmingham, UK. this is the first report of this kind of rotaxane. The principle involves inserting a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate into a large cucurbituril macrocycle as the axle.1 The resulting pseudo-rotaxane is readily converted into a proper interlocked rotaxane by adding branch points to the helicate strands that form the surface of the cylinder (like branches and roots on a tree trunk). The supramolecular cylinder that forms the axle is itself a member of a unique and remarkable class of helicate metallo-drugs that bind Y-shaped DNA junction structures and induce cell death.2 While pseudo-rotaxanation i.e., the capped cylinder without CB10 does not modify the DNAbinding properties, proper, mechanically interlocked rotaxanation transforms the DNA-binding and biological activity of the cylinder. The interesting observation is the ability of the cylinder to de-thread from the rotaxane (and thus to bind DNA junction structures) is controlled by the extent of branching: fully-branched cylinders are locked inside the cucurbituril macrocycle, while cylinders with incomplete branch points can de-thread from the rotaxane in response to competitor and being available for binding to the Y shaped junction binding. The number of branch points can thus afford kinetic control over the drug de-threading and release.
1. Catherine A. J. Hooper, Lucia Cardo, James S. Craig, Lazaros Melidis, Aditya Garai, Ross Egan, Viktoriia Sadovnikova, Florian Burkert, Louise Male, Nikolas J. Hodges, Douglas F. Browning, Roselyne Rosas, Fengbo Liu, Fillipe V. Rocha, Mauro A. Lima, David Bardelang, Simin Liu and Michael J. Hannon " Rotaxanating metallosupramolecular Nano-cylinder Helicates to Switch DNA Junction Binding " J. Am. Chem. Soc. 2020, 142, 20651-20660.
2. Lucia Cardo, Michael J. Hannon “Non-covalent metallo-drugs: using shape to target DNA and RNA junctions and other nucleic acid structures” 5 Feb 2018, Metallo-drugs: Development and Action of Anticancer Agents. Walter de Gruyter GmbH & Co. KG, p. 303-324 22 p.(Metal Ions in Life Sciences; vol. 18).
New Reaction Development
The synthesis of organic molecules has transformed our society, providing medicines, biological probes, crop protectants, food preservatives and components of organic materials. As we advance further into the 21st century, synthetic chemistry will continue to play an important role and will continue to deliver major societal benefits. However, despite significant progress, the problems and difficulties associated with chemical synthesis continue to limit the rate of growth and development of these disciplines. To meet the emerging challenges across new disciplinary boundaries in a rapidly changing scientific landscape we require more rapid and robust techniques for organic synthesis. I plan to address these issues in my research proposal by developing innovative reactions and strategies that enable us to access versatile reactive intermediates for the mild and sustainable synthesis of medicinally relevant compounds. To achieve these ambitious goals, I have divided the research program into three key objectives. 1) Synthesis and applications of α-diazo boronic esters, 2) Ring strain enabled reaction discovery, and 3) Deconstructive functionalizations for drug discovery.
Development of New Methods for Selective and Efficient Chemical Synthesis
In spite of the changing face of chemistry, the impact of chemical synthesis - the ability to make organic molecules in a controlled manner - has not diminished. Nevertheless, the increasingly complex synthetic problems being posed by nature, medicine and organic materials demand new concepts and strategies to meet these challenges. This seminar will describe new methods for selective and efficient chemical synthesis that I have developed in three different research areas: photocatalysis, hypervalent iodine chemistry, and organoboron chemistry. The generation of aryl radicals from aryl diazonium salts needs, in traditional methods, a catalytic or stoichiometric amount of a redox-active transition metal salt. Visible light can provide the required redox energy and has been considered as an ideal reagent for organic synthesis. In the first part, I will discuss the photoredox catalyzed Meerwein arylation. 1 Alkynes are ubiquitous in both naturally occurring and synthetic organic compounds. One of the most often used methods for the synthesis of alkynes consists in the addition of acetylene anions to electrophilic positions of molecules. In contrast, the reversed polarity approach, the addition of alkynes onto nucleophiles, has been less investigated, limiting the structural diversity and potential applications of this important class of compounds. In the second part, I will present electrophilic alkynylation methods using hypervalent iodine reagents.2 In the last part of the seminar, I will discuss my current research on 1,2-metalate rearrangements of boron derivatives to access substituted cyclobutane derivatives.3 This method allows for a rapid and stereoselective synthesis of Grandisol.
1 a) Hari, D. P.; Schroll, P.; König, B. J. Am. Chem. Soc. 2012, 134, 2958. b) Hari, D. P.; König, B. Angew. Chem, Int.
Ed. 2013, 52, 4734. c) Hari, D. P.; Hering, T.; König, B. Angew. Chem. Int. Ed. 2014, 53, 725.
2 a) Hari, D. P.; Waser, J. J. Am. Chem. Soc. 2016, 138, 2190. b) Hari, D. P.; Waser, J. J. Am. Chem. Soc. 2017, 139,
8420. c) Hari, D. P.; Caramenti, P.; Waser, J. Acc. Chem. Res. 2018, 51, 3212. d) Hari, D. P.; Pisella, D.; Wodrich,
M. D.; Tsymbal, A. V.; and Waser. J. Angew. Chem. Int. Ed. 2020, 10.1002/anie.202012299.
3 Hari, D. P.; Abell, J. C.; Fasano, V.; Aggarwal, V. K. J. Am. Chem. Soc. 2020, 142, 5515. b) Hari, D. P.;
Madhavachary, R.; Fasano, V.; Haire. J.; Aggarwal, V. K. J. Am. Chem. Soc.2020, submitted.
Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer's disease brain tissue
Amyloid fibril formation by various polypeptides is a biophysically interesting and biomedically important phenomenon, any understanding of which depends on molecular structural information. The aggregation of amyloid-β (Aβ) peptide in the brain as amyloid fibrils is a pathological hallmark of Alzheimer’s disease. Structural studies of these aggregates are important in understanding their formation, spreading, and for development of therapeutic and diagnostic approaches. In this talk, I will describe the structural studies of Aβ-fibrils from the postmortem brain of an individual with Alzheimer’s disease. Here we have integrated both solid-state NMR and cryo-EM to solve the structure of the most common polymorph of Aβ-fibrils that develop in the brain of Alzheimer’s disease patients. Here we present the cryo-EM map of Aβ-fibril at 2.7 Å resolution. The information from both solid-state NMR and cryo-EM are combined in a single structure calculation to obtain the structure of brain-derived Aβ-fibrils. In the case of Aβ fibrils, we have found a surprising two-fold symmetric polymorph with a mass-per-length value of 27 kDa/nm (indicating three Aβ molecules per β-sheet repeat spacing). The integration of cryo-EM and solid-state NMR pave the way for structural studies of complex systems.