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
Fri, Oct 23, 2015
Fri, Oct 30, 2015
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
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