Upcoming Events

Friday, August 18, 2017

11:00 AM to 12:00 PM Special Seminar - MoSE 3201A - Prof. Christopher Rowley
The Right Method for the Right Problem: Modeling Ions, Membranes, and Covalent-Modifiers
Our group develops new computational methods to study biophysical chemistry, including topics like as membrane permeation, ion-biomolecule binding, and the covalent modification of proteins. In this talk, I will present examples of our recent work on these topics. The first topic is the permeation of gasotransmitters through cell membranes. H2S, CO, and NO are endogenous signaling molecules with potential to be used as anti-inflammatory agents. These molecules are able to permeate cell membranes rapidly without a facilitator. Our simulations show that the small radii and hydrophobicity of these molecules allow them to diffuse freely through membranes, allowing them to react with intracellular targets rapidly [1]. Using a polarizable force field and a model derived from the Generalized Langevin Equation, we were able to predict the rate of permeability quantitatively. Our next subject was the relative solubility of Mg(II) and Zn(II). QM/MM simulations reveal that the greater Lewis acidity of Zn(II) results in its greater solubility. Lastly, we have studied drugs that contain cysteine-targeting electrophiles that form covalent bonds with their targets. A new class of kinase-targeting anti-cancer drugs (e.g. ibrutinib) include an electrophilic acrylamide group that reacts with an active site cysteine residue. By computationally screening hundreds of putative warheads, we found that effective warheads must allow for slow and reversible additions, which avoids non-selective modification of proteins. We have also developed a new computational method to identify acidic cysteine residues that serve as facile targets for covalent modification [3]. [1] Riahi, S., Rowley C.N. Why Can Hydrogen Sulfide Permeate Cell Membranes? J. Am. Chem. Soc. 2014, doi: 10.1021/ja508063s [2] Riahi, S., Rowley C.N. J. Comput. Chem. 2014, doi: 10.1002/jcc.23716 [3] Awoonor-Williams, E., Rowley, C.N. J. Chem. Theory Comput., 2016, doi: 10.1021/acs.jctc.6b00631

Thursday, August 24, 2017

04:00 PM to 05:00 PM Colloquium - MoSE G011 - Prof. Raquel Lieberman
Molecular characterization of myocilin: pathway to new treatments for glaucoma
The Lieberman lab uses biophysical, structural, and chemical biology approaches to characterize proteins involved in conformational disorders and ameliorate the misfolding phenotype. A major research effort in the lab has been investigations of the myocilin, which is implicated in familial cases of the prevalent ocular disorder glaucoma. I will present our efforts toward a detailed molecular understanding of myocilin structure, function, and disease pathogenesis, including striking similarities with amyloid diseases, as well as new directions for glaucoma therapeutics.

Thursday, August 31, 2017

04:00 PM to 05:00 PM Colloquium - MoSE G011 - Prof. Ronghu Wu
Effective MS-Based Chemical and Enzymatic Methods for Global and Site-Specific Characterization of Protein Glycosylation
Protein glycosylation is ubiquitous in biological systems and is essential for mammalian cell survival. Aberrant glycosylation is directly related to multiple human diseases, including cancer and infectious diseases. Glycoproteins contain a wealth of valuable information regarding the developmental and diseased statuses of cells. However, Due to the heterogeneity of glycans, low abundance of most glycoproteins, and dynamic nature of the modification, it is extraordinarily challenging to analyze glycoproteins in complex biological samples. In the Wu lab, they have developed novel mass spectrometry (MS)-based chemical and enzymatic methods to (1) globally analyze glycoproteins in complex biological samples, (2) specifically target glycoproteins only on the surface of human cells, (3) comprehensively quantify glycoprotein and surface glycoprotein dynamics, and (4) selectively characterize glycoproteins with a particular and important glycan. Innovative and effective methods are critical to advance glycoscience research, which will result in better understanding glycoprotein functions, and unraveling the molecular mechanisms of diseases. Global analysis of glycoproteins, especially low-abundance ones, will lead to the discovery of glycoproteins as effective disease biomarkers and the identification of glycoproteins and/or enzymes responsible for aberrant glycosylation as drug targets.

Thursday, September 07, 2017

04:00 PM to 05:00 PM Vasser Woolley Distinguished Lecture - MoSE G011 - Prof. Natalie Ahn
Phosphorylation-regulated protein dynamics in kinase regulation and implications for inhibitor design: The case of ERK2
The MAP kinases, extracellular-regulated protein kinases 1 & 2 (ERK1/2), are important drug targets for cancers caused by oncogenic mutations in RAS and B-RAF. Preclinical studies show that cells from metastatic cancers with acquired resistance to RAF and MKK inhibitors can be effectively killed using small molecule inhibitors of ERK, some of which are in early stage clinical trials. An important unsolved question is: How is ERK2 activated by dual phosphorylation at Thr and Tyr residues, both catalyzed by MKK1/2? Using hydrogen exchange mass spectrometry and NMR relaxation dispersion experiments, we discovered that the activation of ERK2 involves the release of protein motions, leading to global exchange between conformational states which we believe function to enable productive nucleotide binding. An intriguing possibility is that these phosphorylation-regulated dynamics may be coupled to steps in catalytic turnover. Importantly, high affinity ERK inhibitors, which are effective towards cells with acquired resistance, show properties of conformation selection in a manner correlating with slow dissociation. Our findings suggest that the regulated dynamics of ERK2 are exploited by these inhibitors to improve their kinetic properties and efficacy.

Tuesday, September 12, 2017

11:00 AM to 12:00 PM Special Seminar - MoSE 3201A - Prof Ken Hanson
Harnessing Molecular Photon Upconversion Using Self-Assembled Multilayers on Metal Oxide Surfaces
Photon upconversion--combining two or more low energy photons to generate a higher energy excited state--is an intriguing strategy for increasing the maximum theoretical solar cell efficiencies from 33% to greater than 43%. In this presentation we will introduce self-assembled multilayers of sensitizer and acceptor molecules on nanocrystalline metal oxide films as a new structural motif for facilitating molecular photon upconversion via triplet-triplet annihilation (TTA-UC) and directly extracting charge from the upconverted state. Under light intensities as low as ambient solar flux we demonstrate a more than four-fold increase in the short circuit current relative to the sum of the sensitizer and acceptor monolayer devices. We will discuss the dynamics events during TTA-UC, limitations of the current film, and strategies for increasing the TTA-UC efficiency and device performance.

Tuesday, September 19, 2017

11:00 AM to 12:00 PM Special Seminar - MoSE 3201A - Prof Roy Xavier
Molecular Clusters: Building Blocks for Nanoelectronics and Material Design
The programmed assembly of nanoscale building blocks offers exciting new avenues to creating electronic devices and materials in which structure and functions can be chemically designed and tuned. In this context, the synthesis of inorganic molecular clusters with atomically-defined structures, compositions and surface chemistry provides a rich family of functional building elements. This presentation will describe our efforts to assemble such "designer atoms" into a variety of hierarchical structures and devices, and study the resulting collective properties. In one design, single clusters are wired into electrical junctions that can be operated as molecular-scale transistors. The single cluster devices exhibit room-temperature current blockade below a threshold voltage, and they can be "turned on" by applying an electrochemical potential across the junction, enabling the temporary occupation of the cluster core states by sequential transiting carriers. A second area of exploration is in creating solid state materials in which preformed clusters emulate the role of atoms in traditional "atomic" solids. These materials offer a unique opportunity to combine programmable building blocks and atomic precision. As such, they bridge traditional crystalline semiconductors, molecular solids, and nanocrystal arrays by synergizing some of their most attractive features. Recent synthetic advances to develop this concept into a "modular" platform for materials design will be presented. It will be shown that novel, tunable, collective properties (magnetic, optical, electrical and thermal transport) emerge from specific interactions between the building blocks within these assemblies. The programmed assembly of nanoscale building blocks offers exciting new avenues to creating electronic devices and materials in which structure and functions can be chemically designed and tuned. In this context, the synthesis of inorganic molecular clusters with atomically-defined structures, compositions and surface chemistry provides a rich family of functional building elements. This presentation will describe our efforts to assemble such "designer atoms" into a variety of hierarchical structures and devices, and study the resulting collective properties. In one design, single clusters are wired into electrical junctions that can be operated as molecular-scale transistors. The single cluster devices exhibit room-temperature current blockade below a threshold voltage, and they can be "turned on" by applying an electrochemical potential across the junction, enabling the temporary occupation of the cluster core states by sequential transiting carriers. A second area of exploration is in creating solid state materials in which preformed clusters emulate the role of atoms in traditional "atomic" solids. These materials offer a unique opportunity to combine programmable building blocks and atomic precision. As such, they bridge traditional crystalline semiconductors, molecular solids, and nanocrystal arrays by synergizing some of their most attractive features. Recent synthetic advances to develop this concept into a "modular" platform for materials design will be presented. It will be shown that novel, tunable, collective properties (magnetic, optical, electrical and thermal transport) emerge from specific interactions between the building blocks within these assemblies.
11:00 AM to 12:00 PM Meeting - MoSE 3201A - Faculty Meeting
No information available.

Thursday, September 21, 2017

04:00 PM to 05:00 PM Special Seminar - MoSE 3201A - Prof. Hanadi Sleiman
Frontiers in Chemistry: DNA Nanostructures for Cellular Delivery of Therapeutics
DNA nanotechnology can assemble materials on the nanoscale with exceptional predictability and programmability. In a sense, this field has reduced the self-assembly space into a simple 'language' composed of four letters (A, T, G, C). Nature, on the other hand, relies on many more supramolecular interactions or 'languages' to build its functional structures. Over the last 50 years, supramolecular chemistry has taken advantage of these interactions to assemble materials with highly diverse structures and functions. This talk will describe our efforts to merge the field of supramolecular chemistry with DNA nanotechnology. This approach results in new motifs and functionalities that are unavailable with base-pairing alone. Starting from a minimum number of DNA components, we create 3D-DNA host structures, such as cages, nanotubes and micelles, that are promising for targeted drug delivery. These can encapsulate and selectively release drugs and materials, and accomplish anisotropic 3D-organization. We find that they resist nuclease degradation, silence gene expression to a significantly greater extent than their component oligonucleotides and have a favorable in vivo distribution profile. We designed a DNA cube that recognizes a cancer-specific gene product, unzips and releases drug cargo as a result, thus acting as a conditional drug delivery vehicle, as well as DNA structures that bind to plasma proteins with low nanomolar affinities. We will also describe a method to 'print' DNA patterns onto other materials, thus beginning to address the issue of scalability for DNA nanotechnology. Finally, we will discuss the ability of small molecules to reprogram the assembly of DNA, away from Watson-Crick base-pairing and into new motifs.

Tuesday, October 03, 2017

04:00 PM to 05:00 PM Biochemistry Division Seminar - MoSE 3201A - Prof. Abhishek Chatterjee
TBD
No information available.

Thursday, October 05, 2017

11:00 AM to 12:00 PM Analytical Division Seminar - MoSE 3201A - Prof. Abraham Badu-Tawiah
TBD
No information available.

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