IQB and CABM Seminar Series | Fall 2018

Wednesdays 12:00 pm

September 26, 2018

Stephen Burley
Rutgers University
Title: Impact of the Protein Data Bank on Our Understanding of Anti-cancer Drug Action and Mechanisms of Resistance

Location: Proteomics Room 120
Seminar Host: Sijian Wang


Dr. Burley will be available to meet by arrangement on the day of his seminar to discuss areas of mutual interest. Click here to arrange a meeting
The Protein Data Bank (PDB) was established in 1971 as the first open access digital data resource in biology, serving as the single global archive for 3D macromolecular structure data. The PDB currently houses 144,000 atomic level biomolecular structures determined by crystallography, NMR spectroscopy, and 3D electron microscopy. It is managed by the Worldwide Protein Data Bank partnership (wwPDB; wwpdb.org). US PDB operations are conducted by the RCSB Protein Data Bank (RCSB PDB; RCSB.org; Rutgers University and UC San Diego) and funded by NSF, NIH, and DoE. The RCSB PDB serves as the global Archive Keeper for the wwPDB. During calendar 2017, ~680 million structure data files were downloaded from the PDB by Data Consumers working in every sovereign nation recognized by the United Nations. During this same period, the RCSB PDB processed >6200 new atomic level biomolecular structures plus experimental data and metadata coming into the archive from Data Depositors working in the Americas and Oceania. In addition, RCSB PDB served >1 million RCSB.org users worldwide with PDB data integrated with ~40 external data resources providing rich structural views of fundamental biology, biomedicine, and energy sciences, and >600,000 PDB101.rcsb.org educational website users around the globe. RCSB PDB resources for understanding anti-cancer drug action and mechanisms of resistance will be described in detail together with metrics documenting the impact of access to PDB data on basic and applied research, clinical medicine, education, and the economy.
October 3, 2018

William Jorgensen
Yale University
Title: Computer-Aided Discovery of Enzyme Inhibitors   

Location: CABM Room 010
Seminar Host: CABM/IQB

 
October 10, 2018

David Case
Rutgers University
Title: What Can We Learn From MD Simulations of Biomolecular Crystals?

Location: Proteomics Room 120
Seminar Host: Sijian Wang

The adaption of graphical processing units (GPUs) to biomolecular simulations has made microsecond-scale simulations of biomolecular crystals available on a nearly-routine basis.  Typically, a super-cell consisting of several crystallographic unit cells becomes the periodically-repeating unit in the simulation; in this talk, I will consider super-cells with up to 343 unit cells.  Here are some ways this data might be used:
  • Straightforward comparisons between computed and experimental average structures and atomic displacement parameters can be used to identify problems in biomolecular force fields.  
  • Structural fluctuations in the simulations can be used to estimate diffuse scattering intensities, which can be compared to recent measurements using modern detectors.  I will show examples of results for lysozyme in three crystal forms, using data collected at CHESS by Steve Mesiburger and Nozomi Ando as a reference.  These provide important insights into the contributions to diffuse scatter from water and from lattice vibrations of the protein.
  • Force fields can provide restraints for cyrstallographic refinements, and a model for density fluctuations in regions of "disordered" or "bulk" solvent (mainly water).  Such models appear to account for protein and solvent contributions to Bragg intensities in ways that are a systematic improvement over the procedures used in most protein structure refinement protocols.
October 17, 2018

Helen Berman
Rutgers University
Title: Target Zero-Using Film for Medical Education

Location: Proteomics Room 120
Seminar Host: Stephen Burley

 
October 24, 2018

Pei Wang
Icahn School of Medicine at Mount Sinai
Title: Constructing Tumor-Specific Gene Regulatory Networks Based on Samples With Tumor Purity Heterogeneity

Location: Proteomics Room 120
Seminar Host: Sijian Wang

Tumor tissue samples often contain an unknown fraction of normal cells. This problem well known as tumor purity heterogeneity (TPH) was recently recognized as a severe issue in omics studies. Specifically, if TPH is ignored when inferring co-expression networks, edges are likely to be estimated among genes with mean shift between normal and tumor cells rather than among gene pairs interacting with each other in tumor cells. To address this issue, we propose TSNet a new method which constructs tumor-cell specific gene/protein co-expression networks based on gene/protein expression profiles of tumor tissues. TSNet treats the observed expression profile as a mixture of expressions from different cell types and explicitly models tumor purity percentage in each tumor sample. The advantage of TSNet over existing methods ignoring TPH is illustrated through extensive simulation examples. We then apply TSNet to estimate tumor specific co-expression networks based on breast cancer expression profiles. We identify novel co-expression modules and hub structure specific to tumor cells.
October 31, 2018

Lu Wang
Rutgers University
Title: Computational Characterization of Biodegradable Nanoscaffolds and Biological Short Hydrogen Bonds

Location: Proteomics Room 120
Seminar Host: Darrin York

In this talk, I will present our recent computational efforts in characterizing molecular adsorption on biodegradable MnO2 nanoscaffolds and elucidating the structural features of short hydrogen bonds in proteins, with an emphasis on the importance of quantum effects in determining their properties. In the first case, we have focused on the MnO2 nanoscaffolds, which are excellent drug delivery agents for potential applications in advanced stem cell therapy. Combining quantum chemistry calculations and UV-Vis experiments, we have identified the key forces that drive the adsorption of neurogenic drugs on the nanoscaffolds, and proposed a metric that can qualitatively predict the adsorption affinities of cellular regulator molecules based on their structures and chemical compositions. In the second system, we have conducted statistical analysis of the Protein Data Bank to reveal the abundance and structural features of short hydrogen bonds in proteins. We then demonstrate the quantum mechanical nature of these short hydrogen bonds using first principles simulations of an enzyme system.
November 7, 2018

Marcelo Jacobs-Lorena
Johns Hopkins - Bloomberg School of Public Health
Title: What Peptides Taught Us About the Life Cycle of the Malaria Parasite

Location: CABM Room 010
Seminar Host: CABM

 
November 14, 2018

Sagar Khare
Rutgers University
Title: Supervised Learning of a Viral Enzyme Substrate Specificity Landscape Using Deep Sequencing and Molecular Simulations

Location: Proteomics Room 120
Seminar Host: Sijian Wang

 
November 28, 2018

Wei Dai
Rutgers University
Title: Understanding Diatom Thylakoid Architecture by Cryo-Electron Tomography, Automated Annotation and Proteomic Analysis

Location: Proteomics Room 120
Seminar Host: Stephen Burley

The complex evolutionary history of photosynthetic organisms has led to an immense diversity in photosynthetic characteristics and behavior. These changes had been induced by the interplay between environmental factors and the organisms’ physiological needs, often reflecting the biogeochemical history of Earth. Diatoms are a highly successful algae taxon, responsible for about 25% of the world’s photosynthesis. They are secondary symbionts of the “red” algae lineage characterized by a photosynthetic plastid with loosely appressed thylakoids that lack the grana stacking organization evident in the green lineage. Currently, little is known about the macromolecular arrangement of the photosynthetic machinery in diatoms. Here, we integrated proteomic analysis with phase contrast cryo-electron tomography to unravel the molecular architecture of diatom thylakoid membranes, and to resolve 3D structures and dynamics of photosynthetic protein complexes. Although there is no obvious spatial differentiation of diatom’s thylakoid membrane, photosystem II (PSII), the photosynthetic complex catalyzing the light-induced water splitting, exists in two, interchangeable forms, and is heterogeneously distributed on the loosely appressed layers of thylakoids, forming patches of possible functional units. The first form, the holocomplexes, was found to form loose clusters and may serve as anchor points to retain layering of the thylakoid. A more compact form of PSII that is consist of core subunits only assembled into tightly packed 2D crystalline arrays in the open region of the membrane. These observations strongly suggested that diatoms have evolved to spatially segregate their photosynthetic complexes to optimize their photosynthetic electron transport. These structural results underscore a convergent evolution between the “red” lineage diatoms and the “green” lineage higher plants towards a similar functional distribution of protein complexes despite different evolutionary origin and unique thylakoid structural organization.
  December 5, 2018

TBD

Location: CABM Room 010
Seminar Host: CABM

 
December 12, 2018

Biju Parekkadan
Rutgers University
Title: Building High-Throughput Expression Libraries From Genomes

Location: Proteomics Room 120
Seminar Host: Stephen Burley

 With an increasing amount of genetic content being discovered every day, a complimentary technology is required to express genomic regions for functional testing. Here, we present long adapter single stranded oligonucleotides (LASSO) as tool to capture and clone genomic regions in a massively parallel manner. Development of LASSO technology and proof of concept applications in cloning a protein library from the human microbiome will be described.