Chemistry Seminar Schedule
Seminars begin at 3:30 pm on Friday afternoons in Merrill Lecture Room 4, except as noted, and are preceeded by refreshments at 3:15.
Discussion seminars begin at 3:30pm on Friday afternoons in Merrill Science Center Room 315.
Fri, Sep 11, 2015
Fri, Sep 18, 2015
Seminar with Professor John Engen, Northeastern University; Department of Chemistry and Biochemistry
SEMINAR TITLE: "Hydrogen exchange mass spectrometry for the analysis of protein conformation at biological membranes."
ABSTRACT: A continually growing area of mass spectrometry is the analysis of protein conformation and dynamics. One classic approach is to label protein molecules in solution under physiological conditions as the incorporation of the labeling agent is a function of the folded conformation. Hydrogen exchange (HX) methods label the backbone amide hydrogens of proteins with deuterium and the location and magnitude of the labeling can then be determined with mass spectrometry (MS). HX MS studies are particularly well suited for analysis of proteins that will not crystallize, proteins not amenable to NMR, or proteins available in only small quantities. This presentation will explore current methodology and applications of HX MS, both for systems in solution and for the analysis of membrane proteins. Recent development of HX MS methods for the interrogation of peripheral membrane proteins at Langmuir monolayers will be described and illustrated with the analysis conformational changes in the HIV-1 Nef protein upon membrane localization.
SHORT BIOGRAPHY: John R. Engen is a Professor of Bioanalytical Chemistry at Northeastern University in Boston. Professor Engen holds two B.S. degrees (molecular biology and biochemistry) from Union College and a Ph.D. in Chemistry from the University of Nebraska (working with David L. Smith). He completed postdoctoral work at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany and at the Los Alamos National Laboratory. From 2002-2006, he was an Assistant Professor of Chemistry, Biochemistry and Molecular Biology at the University of New Mexico in Albuquerque. In 2012-2013, he was a Visiting Professor of Biochemistry in the laboratory of Prof. F. Ulrich Hartl at the Max Planck Institute of Biochemistry in Martinsried, Germany. Prof. Engen is a Fellow of the European Molecular Biology Organization (EMBO), received the 2009 Arthur F. Findeis Award from the American Chemical Society, and served on the Board of Directors for the American Society for Mass Spectrometry (ASMS) from 2009-2011.
Professor Engen has become a recognized expert in the area of understanding proteins and protein conformation with mass spectrometry. He uses hydrogen-deuterium exchange to probe conformation and dynamics during various activation states. Proteins that are not amenable to mainstream structural techniques such as X-ray diffraction and NMR can be probed with such methods. Such experiments, among other things, can reveal the effects and locations of binding, be diagnostic for proper protein folding, and be used to determine conformational changes during protein function.
Professor Engen has published over 100 papers on the topic of hydrogen exchange in recent years and given hundreds of invited lectures worldwide to academia and industry. He teaches a yearly ASMS short course on protein structural analysis by mass spectrometry. Current research projects in his laboratory include (1) investigations of kinase conformation to understand regulation and aberrant signaling in various disease states including cancer, (2) analysis of the conformation of viral accessory proteins from HIV, (3) studies of protein conformation at biological membranes, and (4) optimization and methods development in hydrogen exchange mass spectrometry.
Fri, Sep 25, 2015
Discussion Seminar for Professor John Engen, Northeastern University; Department of Chemistry and Biochemistry
Seminar Title: "Hydrogen exchange mass spectrometry for the analysis of protein conformation at biological membranes."
Fri, Oct 2, 2015
Mark Boyer and Sangbo Nam presenting:
Mark Boyer ‘16
“Understanding the Argon Vinyl-Chloride Complex through Discrete Variable Representation.”
Abstract: Argon-haloethylene van der Waals complexes can play an import role in understanding intermolecular forces. The structures of these complexes, formed in a supersonic expansion using argon as the carrier gas are significantly influenced by relatively weak, but nevertheless important, dispersion forces, and several display evidence of quantum mechanical tunneling. Discrete variable representation (DVR) is a useful tool in providing a basis for understanding these complexes, as it accounts for the complicated form of the potential energy in a simple manner. However, DVR introduces its own complications in representing the kinetic energy of the complex that need to be dealt with before it is possible to understand fully a complex such as argon vinyl-chloride.
Sangbo Nam ‘16
“Targeting a Cryptic Allosteric Site for Selective Inhibition of the Oncogenic Protein Tyrosine Phosphatase Shp2.”
Abstract: Targeted covalent inhibition is a growing field of drug discovery in which molecules are covalently bound to the target protein for increased potency and residence time. Protein tyrosine phosphatase (PTP) Shp2 is a desirable target for inhibition due to its role in Leopard and Noonan syndromes as well as sporadic juvenile myelomonocytic leukemia. This study aims to discover a molecule that covalently binds to a recently discovered cryptic allosteric site on Shp2, C333, which is not conserved in most other PTPs. A variety of acrylate derivatives, which can bind covalently to cysteines through a Michael addition, will be synthesized and incubated with WT and C333P Shp2. Their activities will then be tested with a phosphatase activity inhibition assay. A molecule that is able to inhibit WT, but not C333P Shp2 will be a likely candidate for selective inhibition of Shp2's allosteric site.
Fri, Oct 9, 2015
Fri, Oct 16, 2015
Jovan Damjanovic, Asher Lichtig and Xiao Xiao presenting:
Jovan Damjanovic '16
“Elucidating Protein Folding Pathways using Computer Simulations of Hydrogen Exchange Mass Spectrometry Experiments.”
Abstract: One of the most widely studied phenomena in modern biochemistry is that of protein folding. The conformations that proteins can assume, and the thermodynamic and kinetic pathways that govern the transition between these conformations, have vital significance for proteins’ biological functions. Protein misfolding and destabilization have also been implicated in many high-profile diseases, such as Alzheimer’s, Parkinson’s, and ALS among others. Hydrogen exchange mass spectrometry (HXMS) is a technique that enables us to study these pathways under near-native conditions, addressing one of the most severe drawbacks of prior experimental techniques, which required denaturation to extract folding parameters. Being able to simulate HXMS time courses and compare the simulation results to experimental data can provide valuable information about how well a proposed folding model matches the given protein, as well as predict values for folding parameters such as relevant rate constants and number of exchange-competent sites. We developed a numerical simulations approach that utilizes the Gillespie algorithm to simulate the folding of a protein as a continuous-time Markov process and check the accuracy of the fit to the experimental data in real time, while iteratively optimizing all of the folding parameter estimates to reach the best fit values. Among other results, this yielded the discovery of a potentially novel high-energy intermediate in the folding of beta 2 microglobulin, and the development of a 3-state folding model for this particular protein.
Asher Lichtig '16
"Synthesis of Polymer-Clay Nanocomposites with Ionically Bound Initiators."
Abstract: In previous years the Burkett lab has created polymer-clay Nanocomposites with the polymer grown from initiators bound directly to the clay. However the Polymer could not be fully characterized as it was contently bound to the clay and could not be removed. My research is in using initiators that are ionically bound to the clay to allow for removal and full characterization of the polymer after polymerization is complete. To do this layered double hydroxide clay is used with anionic initiators.
Xiao Xiao '16
"Synthesis of polymer–clay nanocomposites with a photo-cleavable linkage."
Abstract: Polymer–clay nanocomposites have the potential to combine the flexibility of an organic polymer and the mechanical strength and thermal stability of the clay. These enhanced mechanical properties are desirable for a wide variety of applications in fields ranging from aeronautical engineering to biomedical materials to drug delivery. This thesis aims to develop a synthetic magnesium silicate clay containing an o nitrobenzyl alcohol group that can serve as an initiator for polymerization. The resulting o nitrobenzyl ester linkage to the polymer terminus is capable of undergoing a photo-cleavage reaction under UV radiation, which allows the polymer chains to be cleaved from the clay surface for subsequent study of the properties of the organic polymer chains. Current research direction includes attachment of a silicon-bearing group onto the nitrobenzene via SN2 substitution or amide formation.
Fri, Oct 23, 2015
Nicolas Pascual-Leone and Christine Rehr presenting:
Christine Rehr '16
Seminar Title: “Elucidating Phytoestrogen Function in Plants and Animals”
Abstract: The activation and inhibition of estrogen receptors has many significant physiological effects in humans, whether promoting normal growth and development or causing the proliferation of cancerous tumors. Due to the lack of specificity of these receptors, many compounds can affect their activity in addition to the endogenous estradiol, such as many manmade and natural chemicals that bind to the receptors and can cause varying downstream effects. Therefore, identifying these various compounds and learning more about their functions is very important for human health. The focus here will be specifically on analyzing phytoestrogens, as these plant-based compounds are present in many foods and commercial products, and some are already known to affect diseases such as cancers. In this thesis, phytoestrogens will first be identified and then analyzed for their possible effects in plants and on human estrogen receptors. The compounds will be identified from an analysis of the results of a high-throughput study performed by different US governmental agencies. The chemicals will then be tested for their relative binding affinity to the human estrogen receptor beta, the dominant receptor affected by phytoestrogens, using a fluorescence polarization assay. After identifying compounds that bind sufficiently to the estrogen receptor, functional assays will then be performed by introducing the phytoestrogens into recombinant yeast cells to characterize their agonistic or antagonistic behavior.
Nicolas Pascual-Leone '16
“Electron or Energy Transfer: A Study into the Mechanism of the Excited State Deactivation of Ruthenium Complexes with Ferrocene Derivatives”
Abstract: Ferrocene has been said to be the benzene of organometallic chemistry because it was the first pure hydrocarbon derivative of iron. This iron has the ability to perform a quasi-reversible oxidation, which has sparked much interest into areas of catalysts, non-linear optics, and electrochemistry. Along with these areas, the photochemical behavior of ferrocene has been investigated. Because ferrocene can be used as an excited state quencher, the interactions between it and other molecules has become of great interest. The Young lab has been focused on the excited-state interactions of ruthenium polypyridyl derivatives with various ferrocene complexes, with particular interest in understanding the mechanism of the interaction. There has been much debate over whether the quenching mechanism is Dexter energy or electron transfer. Since these two mechanisms produce different products, experimental confirmation of the products can determine the true path. Transient Absorption (TA) Spectroscopy is being used to view these products. TA Spectroscopy uses laser pulses to excite the compound and measures the change in absorption between the ground state and excited state. It is through the analysis of this change in absorption that we will be determining the mechanism of these interactions.
Fri, Oct 30, 2015
Eleanor Cory and Hannah Tandon presenting:
Eleanor Cory '16
Seminar Title: "Encapsulating C60"
Abstract: Recent research has found that N,N'-amino-acid substituted naphthalenediimide (or NDI) derivatives spontaneously form nanotubes and nanocapsules held together by hydrogen bonds. These tubes and capsules can enclose C60 and C70, respectively, when formed in their presence. The Hansen laboratory hascovalently linked three NDI derivatives to make a trimer, which forms capsules that perfectly encapsulate C60. While the capsules also form when no C60 is present, it appears that enclosing C60 stabilizes the capsule, making it less likely to fall apart than its empty counterpart. The linked NDI trimer contains afunctionality that can be substituted with a number of amino acids or other molecules without altering the capsule shape. This flexibility allows for modification of the polarity of the capsule, with the ultimate goal being the development of a capsule that could allow C60 to be solubilized in water.
Hannah Tandon '16
Seminar Title: "Structure Determination of the (Z)-1-chloro-2-fluoroethylene – HCl Complex Using Microwave Spectroscopy."
Abstract: The Leung Lab utilizes microwave spectroscopy to study the forces between haloethylenes and simple protic acids. As part of this systematic study, the complex between (Z)-1-chloro-2-fluoroethylene and HCl is being characterized using a combination of theoretical and experimental techniques. The lowest energy conformation predicted by theory for the complex is nonplanar with HCl in the ClCCF cavity where the hydrogen of HCl is oriented nearly perpendicular to the plane of the ethylene. This structure is consistent with the structure of the similar complex between vinyl chloride and HCl and seems to indicate a trend for chloroethylenes binding HCl in a nonplanar conformation. Further experimental spectroscopic work will refine the geometry and help characterize the interplay of electrostatic and dispersion forces with steric effects that ultimately leads to the geometry of the complex.
Fri, Nov 6, 2015
Fri, Nov 13, 2015
SEMINAR TITLE: "Methylation of Oxygen Nucleophiles with Safe, Stable Methylating Agents."
RESEARCH INTERESTS: Organic and bioorganic chemistry. We have two major research interests. 1) Selective chemical catalysts and reagents are needed for the modification and functional perturbation of molecules in complex contexts, such as in biological and environmental samples. We use tools from synthetic chemistry and molecular biology to develop new reagents that selectively transform one component of a biological mixture. 2) Methylation reactions are ubiquitous in synthetic organic chemistry, but typical methods rely upon hazardous and/or unstable reagents. We are developing new strategies for methylation and related reactions that instead use safe, stable reagents.
Fri, Nov 20, 2015
Today - Fri, Nov 27, 2015
Fri, Dec 4, 2015
Discussion Seminar for Professor Amy Deveau, University of New England, Department of Chemistry and Physics
Seminar Title: TBD