Title : Protein Crystallography at SPring-8
Title : Nitric Oxide Reductases: Molecular Evolution of Respiratory Enzymes and Global Environment
Nitric oxide reductase (NOR) is an integral membrane protein that is involved in microbial denitrification, a type of anaerobic respiration in which nitrate is reduced in a stepwise manner to dinitrogen (NO3-→ NO2-→ NO → N2O → N2). In this process, NOR catalyzes the reduction of nitric oxide (NO), which is generated as an intermediate product in this process, to nitrous oxide (N2O) using two protons and two electrons (2NO + 2H+ + 2e- → N2O + H2O) via N-N bond formation and N-O bond cleavage at a binuclear center consisting of heme and non-heme iron (FeB). The product of the NOR-catalyzed reaction, N2O, is a greenhouse gas that is 310 times more powerful than carbon dioxide, and is also an ozone depleting substance. Since the use of nitrogen-based fertilizer increases global N2O levels by stimulating the action of soil denitrifiers, NOR is an important topic of study with respect to the global environment. NOR also has clinical and pharmaceutical importance, as evidenced by the fact that some pathogens use NOR to detoxify cytotoxic NO produced by macrophages in immune system of a host. In addition, it has been believed that NOR shares the same ancestor proteins as cytochrome c oxidase (CCO), which is an aerobic respiratory enzyme catalyzing the O2 reduction (O2 + 4H+ + 4e- → 2H2O) at a binuclear center consisting of heme and copper (CuB). Recently, we succeeded in structural determination of NOR in the resting, reduced and ligand-bound states. In the lecture, I will show the molecular mechanism of the NO reduction catalyzed by NOR, which was proposed on the basis of their molecular structures, and discuss the structural and functional characteristics of NOR in relation to the molecular evolution of the respiratory enzymes by comparing them with those of CCO.
Title : Investigations of Thermal Properties of Carbon Nanotubes Using Ramen Spectroscopy and Molecular Dynamics Simulations
Single-walled carbon nanotubes are cylindrical tubes formed from covalently bonded carbon atoms and are described mathematically by performing a rolling operation on the honeycomb planar lattice of a single graphite layer. In the current study, we have examined closely the thermal expansion properties of these quasi one-dimensional objects using experimental Raman spectroscopy and Molecular Dynamics simulations. The Raman measurements have been performed employing a Thermo Scientific DXR spectrometer and a heated cell over a range of temperatures (27-200 deg C), while the Molecular Dynamics simulations utilize the powerful and versatile software package - Large-scale Atomic Molecular Massively Parallel Simulator (LAMMPS). Intriguing results from both experimental measurements and simulation studies help to shed new light on the thermal properties of carbon nanotubes and have important ramifications for their use in electronic devices.
Title:Structure-function of dystrophin and utrophin in muscular dystrophy
Muscular dystrophy refers to a group of degenerative diseases that cause progressive muscle weakness. Duchenne/Becker muscular dystrophy accounts for more than half of all known cases. Symptoms that include constant falling, waddling, and outturned knees appear as early as age two. During the extreme phase, patients are unable to sit upright, move their arms or legs, or breathe on their own. Patients' life spans rarely exceed early to mid-twenties due to cardiac or respiratory failure. Genetic mutations in a vital muscle protein dystrophin trigger the disease. Utrophin is the closest homologue of dystrophin, and is being investigated as a possible replacement therapy to treat patients. In this talk, I will discuss the molecular mechanisms of the disease trigger and treatment at the fundamental protein level. Such knowledge will ultimately lead to the development of more effective therapies, which include engineered proteins and small molecules.
Title : Role of Protectants and Denaturants in Polymers and Proteins: Insights from Computer Simulation
Longstanding mechanistic questions about the role of protectant Trimethylamine N- oxide (TMAO) which favors protein folding and the denaturant Urea are addressed by studying their effects on the folding of a model polymer chain. Using atomistic molecular dynamics simulations, we show that TMAO and Urea solutions act dramatically differently on these model polymer chains. Their behaviors are sensitive to the strength of the attractive dispersion interactions of the chain with its environment: when these dispersion interactions are high enough, TMAO suppresses the formation of extended conformations of the model polymer as compared to water, while urea promotes formation of extended conformations. Similar trends are observed experimentally on real protein systems. Quite surprisingly, we find that both protectants and denaturants strongly interact with the model polymer, seemingly in contrast with existing explanations of the effect on proteins. We show that what really matters for a protectant is its effective depletion as the polymer conformation changes, which leads to a negative change in the preferential binding coefficient, while the reverse is true in case of denaturant. Finally, we show our results on a simple model polymer is in reasonable agreement with a recent single molecule experiment on a synthetic polymer called polystyrene
Title : Simulating at Multiple Scales: Application to Chemistry and Biophysics
The chemical and biological processes are complex and intriguing in nature. Understanding the mechanisms and implications of these processes requires consideration of the aspect of diverse length and time scales associated with them. In this respect, computer simulation is gaining attention as one of the promising tools. In this presentation, I will highlight certain problems of chemical and biophysical relevance, which I have addressed using computer simulation at different scales. The problems will involve visiting the kinetics of ligand-protein binding at nano-scale, looking at collective behavior of peptide-membrane interaction at an intermediate scale and understanding self-assembly of materials at a large scale. One of the purposes of this talk will be rationalizing the usage of models at different resolution and different simulation techniques to access the diverse spatial and temporal aspects inherent in those problems. The mechanistic insights learnt from the simulations will be discussed and will be compared against relevant experimental inputs. Finally, future directions will be briefly discussed.
Title : to be announced
Title : To be announced
Title : Molecularly resolved single cell:diagnostics andin vivo imaging
The ability to analyze as well as spatially resolve protein signaturesat single cell resolution is becoming increasingly important in biological research, forensic science as well as in clinical diagnostics.This talk will focus on detailing approaches for single cell isolation to single cell protein signature analysis.A method based on DNA barcoding of cellular proteins will be described for rapid, quantitative and multiplexed detection of scant proteins and antigens in single live cell. I will also describe novel imaging techniques for molecularly resolving and mapping protein signatures in vivo.
Title :Chemical approaches and nanoparticle technologies in biology: from live cell imaging to programming biology
Tailoring the properties of nanomaterials by employing chemical tools is crucial for their potential applications in various biomedical research. In this talk I will detail my research on integrating photochemical and synthetic supramolecular chemical tools with nanomaterials for developing state-of-the-art molecular imaging techniques and creatingnovel sensing and therapeutic approaches.Additionally, I will describe an in vivo translation of light regulated system for programming biology, where we havecreated an optochemogenetic switch to regulate temporal- and cell-specific gene expression in mice.
Title : Coupling of Computational and Experimental Methods to Solve Real World Problems: From Reactive Intermediates to Green Chemistry
Reactive intermediates are key elements of almost all facets of chemistry, thus, their identification and characterization is of utmost importance. Computational and experimental efforts to characterize early events in the photochemistry of various carbonyl azides will be presented in this seminar. In particular, discussion will be focused on the observation of excited states of carbonyl azides, and dynamics of their decompositions leading to both singlet caronylnitrene and corresponding isocyanate isomer. Furthermore, attempts to observe vinylidene for the first time by femtosecond absorption spectroscopy will be summarized along with excited state calculations.
The seminar will conclude with the current research efforts in green chemistry and environmental sciences along with future research plans and possible research partnerships to establish a sustainable research group.
Title : Development of Chemical and Biological Therapeutics against Chemical Warfare Poisoning: Butyrylcholinesterase and Paraoxonase-1
Chemical warfare agents, in particular, organophosphorus (OP) compounds continue to pose severe threats to civilian and military personnel as there are no known permanent treatments available that works against all of the OP compounds. Recent usages of such weapons of mass destruction have raised the severity of this problem even further. This presentation will focus on computational and experimental efforts to design possible chemical and biochemical therapeutics against OP exposure. Efforts to utilize Butyrylcholinesterase (BuChE) as a drug against nerve agents will be summarized briefly. Computational insights into the rational engineering of Paraoxonase-1 (PON1) as a scavenger of OP compounds will also be discussed. In particular, the focus will be on developing a binding model, variant design at H115 and K192 positions to increase the efficiency, and possible operating mechanism of PON1. Furthermore, as the active site of PON1 is not known; thus, development of a photo-affinity label for labeling of PON1 by means of excited state calculations and time-resolved spectroscopic methods will be summarized.
Seminar by Prof. John F. Ogilvie, Simon Fraser University, Canada
Title : The Quantum and Chemistry
We distinguish between quantum laws and quantum theories. With
prototypical systems a canonical linear harmonic oscillator and a hydrogen
atom, we illustrate the application of a few methods to calculate the
properties of these systems, emphasizing the applicability of mathematical
Seminar by Prof. John F. Ogilvie, Simon Fraser University, Canada
Title : Photochemistry of Methane at 3 K
We have subjected pure solid methane and methane dispersed in solid
neon, all at 3 K, to irradiation from a synchrotron in the wave length
range 120 - 165 nm, and recorded the infrared spectrum of the products
as a function of wave length of irradiation, molar fraction of methane
in neon and cumulative duration of photolysis. Some thirty products
are identified, including such free radicals as CHn, 1 <= n <= 5, and
carbon chains up to C20. The mechanism of the reactions is discussed.
DCS Annual Talks