TIFR
Department of Chemical Sciences
School of Natural Sciences

Calender

November 8, 2017 at 2.30 pm in AG-80

Title :

Chemical Detoxification of Neurotoxic Methylmercury by Smart Molecules

Abstract :

Methylmercury (MeHg+) is considered to be the most toxic form of mercury due to its ability to accumulate in fat tissues leading to its bio-magnification within the food chain. The toxicological implications associated with the ingestion of MeHg+ may also differ according to its chemical form.1 All seafood, mainly fish, contains mercury, primarily in the form of methylmercury. Consumption of mercury contaminated fish on a regular basis therefore could cause adverse neurodevelopmental, cardiovascular, and immunological health effects. High levels of mercury in fish stocks have been found in mining (Singrauli region in MP and Sonbhadra district in UP), and coastal areas, particularly Ulhas River Estuary and Thane Creek areas, Mumbai (mercury levels in fish from these contaminated areas: 0.89-1.78 mg total Hg/kg dry weight (dw); crabs had 1.42-4.94 mg total Hg/kg dw mercury compared to the permissible limit of 0.5 mg/kg).

 

In nature, however, several microorganisms have been reported as being MeHg+ tolerant due to their ability to convert highly toxic MeHg+ to either less toxic volatile elemental mercury, Hg0 or biologically inert insoluble HgS (metacinnabar). For instance, bacterial organomercurial lyase (MerB) catalyzes the protolytic cleavage of the otherwise inert Hg-C bond of MeHg+ and produces methane (CH4) gas and ionic mercury Hg2+, while a second enzyme mercuric ion reductase (MerA) reduces the product Hg2+ to volatile Hg0. On the other hand, several sulfate reducing bacteria (SRB) convert highly toxic MeHg+ to less toxic insoluble HgS(s) by producing H2S during metabolism.3 In addition, insoluble mercury selenide (HgSe) particles have also been found in a wide range of tissues of marine mammals (whales and dolphins) and also detected in various organs (kidney, liver, muscle, and brain) of humans exposed to MeHg+. HgSe is considered to be much less toxic than mobile, soluble MeHg+ species including MeHgCys and MeHgSG. In this talk I will mainly focus on how small organic molecules can be used intelligently to detoxify highly neurotoxic methylmercury by two distinct pathways, similar to those observed in nature.4-8

 

References:

 

  1. Harris, H. H. et al. Science 2003, 301, 1203; Stern, A. H. et al. Science 2004, 303, 763–766; Korbas, M. et al. ACS Chem. Biol. 2012, 7, 411–420.
  2. Menon, J. S. Indian J. Mar. Sci. 2013, 42, 812; Report of Centre for Science and Environment (CSE), 2012; Deshpande. A et al. Environ Monit assess 2009, 159, 493.
  3. Baldi, F et al. Appl. Environ. Microbiol. 1993, 59, 2479; Clarkson, T. W. et al. Crit. Rev. Toxicol. 2006, 36, 609; Benison, G. C. et al. Biochemistry 2004, 43, 8333; Hong, B. et al. Biochemistry 2010, 49, 8187; Omichinski, J. G. et al. J. Biol. Chem. 2009, 284, 938;
  4. Roy, G. et al. Angew. Chem., 2015, 127, 9455; Angew. Chem. Int. Ed., 2015, 54, 9323. This work is highlighted in Cover Page; Angew. Chem., 2015, 127, 9551; Angew. Chem. Int. Ed., 2015, 54, 9419.
  5. Roy, G. et al. Chem. Eur. J, 2017, 23 (24), 5696. This article is highlighted in "Frontispiece" and considered as "Hot Paper"
  6. International Patent filed (PCT): WO2017168451. 
  7. Roy, G. et al. Inorg. Chem. 2017, xx, xxxx (DOI: 10.1021/acs.inorgchem.7b01301). 
  8. Roy, G. et al. Inorg. Chem. 2017, xx, xxxx (DOI: 10.1021/acs.inorgchem.7b01048).

 

October 30, 2017 at 4.00 pm in AG-69

Title :

Insights into the mechanical properties of polymers by probing their functional group, and segmental motions using solid-state NMR

Abstract :

Predicting mechanical properties like ductility of polymers is, in general, a very difficult problem. However, it is well known that ductility of a single component amorphous glassy polymer is related to the inter- and intra-molecular cooperative segmental motions that occur in the glassy state. These, in turn, are related to the motions of functional groups in the repeat unit of the polymer. In the case of semi-crystalline polymers, the morphology, in addition is also very crucial to the mechanical property of the polymer.

In this talk the results from a study of functional group, and segmental motions in amorphous and semi crystalline polymers using solid-state nuclear magnetic resonance (SSNMR) will be presented. The separated local field NMR has been used to probe the functional group motion. The Center Band only Detection of Exchange (CODEX) experiments have been used to probe the slow segmental motions. We have carried out studies on polycarbonates and polysulfones which are  purely amorphous. Results from the studies carried out on polyoxymethyline, a semi-crystalline polymer will be presented. In this study we have shown that the mechanical property is closely linked to the morphology of this polymer.

October 27, 2017 at 10.00 am in AG-66

Title :

Control of Actin Assembly by Polyphosphoinositides

Abstract :

Polyphosphoinositides (PPIs) such as phosphatidylinositol (4,5) bisphosphate (PIP2), are phospholipids that control many cellular events and bind to dozens of intracellular proteins, including many regulators of the actin-based cytoskeleton.  How phosphoinositides affect their ligands is much less understood than are the mutations that produce abnormal PPI production, but defining how these lipids exert their biological control at the membrane-cytoskeletal interface could lead to new approaches to limiting or reversing the abnormal function of these lipids in disease. The large number of proteins characterized as ligands for PPIs, usually PI(4,5)P2, suggests that specificity within the cell might be attained by changing the physical state of the lipid within the membrane, in addition to its local or global concentration. Recent experiments show that cholesterol-induced redistribution of PIP2 in the lipid bilayer strongly alters its ability to inhibit the actin severing protein gelsolin at constant total PIP2 concentrations and that nucleation of actin polymerization in brain extracts occurs preferentially from liquid disordered membrane domains and from 80 nm PIP2 clusters that form in the presence of µM Ca2+. These results suggest that PPI lateral distribution within cell membranes is structured by cholesterol and divalent or multivalent counterions and affects PPI interactions with the myriad of proteins they appear to regulate in vivo.  Therefore reagents that bind PIP2 and alter its distribution the cell can have important effects on cell function and potentially practical applications.

October 16, 2017 at 4.00 pm in AG-69

Title :

Structural Aspects of Ferritin Protein Cage for Designing Inorganic Biomaterials

Abstract :

Ferritin is a self-assembled 24-mer spherical cage shaped iron storage protein which has an internal cavity of diameter 8 nm. The internal cage is connected with several symmetric pores and interestingly, small metal complexes and organic molecules can easily pass through these pores. The cage is very stable up to 80ºC but disassembles beyond the pH range of 2-11 which can reassemble again at neutral pH. This interesting feature is useful for incorporating larger molecules into the cage. Although the disassembly-reassembly mechanism of ferritin cage has been studied using various spectroscopic and analytical methods, it remains challenging to have a direct structural insight into this mechanism. We used high-speed AFM to observe the phenomena at single molecule level in real-time scale. Due to unique structural features, the ferritin cage is widely utilized for preparing uniform metal nanoparticles which have important catalytic and biomedical applications. For example, magnetic iron oxide nanoparticles grown inside ferritin cage can promote catalytic reactions in the cell and can target and visualize cancer cells. Despite many promising applications, it remains challenging to explore the basic structural features of protein-nanoparticle interactions. In this context, we promoted the chemical reduction of gold ions within a crystalline ferritin cage and analyzed the X-ray crystal structures at various steps. This gives a direct visualization on the formation of gold nanocluster in protein environment and is considered to be an intermediate stage of nanoparticle growth. In another aspect, multiple metal complexes were incorporated simultaneously into the ferritin cage to construct protein-based microcompartment similar to bacterial microcompartment where several enzymes work together for metabolic functions. We studied the X-ray crystal structures and performed the catalytic cascade reactions in confined ferritin environment as a proof of concept. 

 

This presentation includes various structural aspects of metal immobilized ferritin protein cage with X-ray crystal structure analysis and their applications in catalysis as well as understanding the growth of metal nanoparticles in protein environment.   

  

References: 

 

(1) G. Jutz, P. van Rijn, B. S. Miranda, A. Böker. Chem. Rev., 2015, 115, 1653-1701. (2) E. C. Theil, T. Tosha, R. K. Behera, Acc. Chem. Res., 2016, 49, 784-791. (3) B. Maity, K. Fujita, T. Ueno. Curr. Opin. Chem. Biol. 2015, 25, 88-97. (4) B. Maity, K. Fukumori, S. Abe, T. Ueno. Chem. Commun. 2016, 52, 5463-5466. (5) B. Maity, S. Abe, T. Ueno.  Nat. Commun, 2017, 8, 14820. (6) S. Abe, B. Maity, T. Ueno. Chem. Commun. 2016, 52, 6496-6512. 

 

 

October 12, 2017 at 2.30 pm in AG-80

Title :

Development of Heterojunction Based Photocatalysts for Hydrogen Evolution Reaction and Dye Degradation Applications

Abstract :

Due to the increasing industrialization and population growth, energy crises and environmental pollution have become major challenging problems to the human society in the 21st century. Photocatalysis gain immense interest in the field of green energy as a photoconversion technology of converting solar fuel to chemical fuel. The rapid recombination of photogenerated charge carriers, poor light absorption and lack of satisfactory visible light active materials are the major hurdles for single component system to achieve descent photocatalytic activity under solar light. 

 

This presentation will address our investigations of how the heterojunction based photocatalysts (metal/semiconductor-semiconductor) has constructive effect on the photocatalytic activity and overcomes drawbacks of single component photocatalysts. The main part of the work is to enhance the separation and transfer efficiency of photogenarated charge carriers and improve visible light absorption. In order to do this we have synthesized different heterojunction based photocatalysts Pd-SrIn2O4-TiO2, Pd-CdS@CdO-TiO2, In2S3-gC3N4 and ZnCo2O4 marigold flowers and investigated their photocatalytic activity for hydrogen evolution reaction and dye degradation applications. We found that heterojunction based photocatalysts exhibit the enhanced photocatalytic activity as compared to its individual parts. This enhancement may be due  to  the  combined  effect  of  increased visible light absorption, separation and transfer efficiency of photogenerated charge carriers, effective surface area and  co-catalytic  effect  of  Pd  NPs  through  the  formation  of   Schottky  junction. The structural, morphological and optical properties were studied using XRD, RAMAN, XPS, SEM, TEM and UV-Vis spectroscopy. Time resolved PL spectroscopy, photocurrent and electrochemical measurements were used to study the photoinduced charge-transfer in the composite samples. The band potentials were calculated from Mott-Schottky plot and UV-Vis spectroscopy. Based on the band potentials, probable charge transfer schemes in binary and ternary heterojunction photocatalysts were also proposed. The photocatalytic activity of these heterojunction photocatalysts were also investigated for dye degradation application. To investigate the degradation reaction mechanism in depth, the active species formed during the reaction process and pH dependence were studied.

 

September 26, 2017 at 2.30 pm in AG-66

Title :

Molecular Simulation of Long Time Structural Evolution in Nanomaterials

Abstract :

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.

September 25, 2017 at 4.00 pm in AG-69

Title :

A tale of two proteins: What folding dynamics can tell us about the function of structurally similar proteins 

Abstract :

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.

 

September 18, 2017 at 4.00 pm in AG-69

Title :

Coordination Chemistry of Cyclic Peptides: Possible Biological Functions of the Patellamides 

Abstract :

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.

September 15, 2017 at 2.30 pm in AG-80

Title :

Nonribosomal Polyamides Binder Discovery of Ebola Glycoprotein

and

Development of a Platform for Peptidomimetic Covalent Binder Discovery

Abstract :

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.

 

September 14, 2017 at 2.30 pm in AG-80

Title :

Application of Iminoboronate in Chemistry and Biology

Abstract :

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 [1]. 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 [2] along with an unprecedented bioorthogonal reaction [3]. 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 [4].

 

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.

 

September 11, 2017 at 4.00 pm in AG-69

Title :

Bio-nanoconjugation of Mutant Cytochrome P450cam (CYP101) for electro-biocatalysis

August 28, 2017 at 4.00 pm in AG-69

Title :

Dipole Organization and Membrane Biophysics: A Tale of Two Studies

Abstract :

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.

References:

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.   

 

 

August 10, 2017 at 4.00 pm in AG-80

Title :

Physico-chemical Aspects of Synthesis, Characterization of Nanostructured Materials and its Biological Applications

Abstract :

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.

August 3, 2017 at 4.00 pm in AG-80

Title :

The role of conformational dynamics in molecular recognition

Abstract :

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) [1]. 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 [1]. 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 [2]. 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 [2]. 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) [3] 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 [4]. The mechanism of Esyt has importance in understanding the axon degeneration in genetic diseases hereditary spastic paraplegia (HSP) [5] and amyotrophic lateral sclerosis (ALS) [6].

 

Reference:

 

1.Chakrabarti et al. (2017) Structure 25 794-805.

2.Khersonsky & Tawfik (2010) Annu Rev Biochem. 79 471-505.

3.Schauder et al. (2014) Nature 510 552-555.

4.Min et al. (2007) PNAS (USA) 104 3823-3828.

5.Blackstone (2012) Annu Rev Neurosci. 35 25-47.

6.Teuling et al. (2007) J. Neurosci. 27 9801-9815.

 

August 2, 2017 at 11.30 a.m.in AG-80

Title : 

Conformational selection in a protein-protein interaction

Abstract :

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) [1]. 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 [2]. 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.  

 

Reference:

 

1. Changeux & Edelstein (2011) F1000 Biol. Rep. 3 19.

2. Chakrabarti et al. (2016) Cell Rep. 14 32-42.