The David L. Weaver Endowed Lecture Series in Biophysics and Computational Biology is dedicated to the memory of David L. Weaver, a prominent biophysics researcher and professor at Tufts University.
About Dr. Weaver
Dr. Weaver made significant contributions to the understanding of protein folding. He was impressed with the research and faculty at the UC Davis Genome Center, where he was planning to spend his sabbatical year 2006–2007.
Dr. Weaver focused his early research on high-energy physics, studying photon production and elementary particles. After spending a year and a half as a NATO Fellow at the European Center for Nuclear Research (CERN), in Geneva, Switzerland, he returned to Tufts and began to think about how he could apply his physics background to problems in biology. While he continued to make significant contributions in high-energy physics, for which he received tenure at Tufts in 1969, Dr. Weaver’s interests continued to shift towards some of the key unsolved problems in biology. At the University of Rome, Italy, as a visiting CNN Fellow at the Frascati National Laboratory, he became more and more interested in applying his mathematical skills to gain a better understanding of molecular dynamics. He visited Dr. Martin Karplus at Harvard during a sabbatical in 1972, and they began a collaboration that culminated in a paper about a then theoretical diffusion-collision model for protein folding (Nature, 1976). The Diffusion-Collision Model was ahead of its time because the data needed to test it were not available when it was published in 1976. But by the mid-1990s experimental studies had shown that the model did indeed describe the folding mechanism of many proteins. The field has been completely transformed in recent years because of its assumed importance for understanding the large number of protein sequences available from genome projects, says Karplus, and because of the realization that misfolding can lead to a wide range of human diseases.
Dr. Weaver received grants from NASA, NATO, Bruker Optics, and the NIH to establish computer facilities at Tufts where he continued to work with students, Dr. Karplus and other collaborators to improve his understanding of important biophysical problems. He was a regular visitor at labs overseas and in the United States, and he authored or co-authored a number of significant scientific publications.
He held degrees in Chemistry from Rensselaer Polytechnic Institute and in Physical Chemistry from Iowa State University. A Fellow of the American Physical Society, Dr Weaver also served as the chair of the Tufts Department of Physics and Astronomy from 1989 to 2002. He was born in Albany, NY, on April 18th, 1937.
David Weaver possessed an easy manner, a sense of fairness, curiosity and an enjoyment of life that was evident in his teaching and relations with colleagues. All who knew him will miss his kind and cheerful humor, his smile and his generous spirit.
The 2017 Lecture: Professor Angela M. Gronenbron —‘Synergy between NMR, cryo-EM and large-scale MD simulations – An all atom model of a native HIV capsid.’
Date: Monday, April 3rd 2017, 3pm, GBSF 1005.
HIV and other retroviruses use a Trojan horse style of infection, taking advantage of a cloak that shields its genome till the time is ripe to open the shield. Once HIV gets inside the cell, it takes over the cellular machinery, turning it into a factory for its own reproduction. This entails a derailment of the normal host defense pathways, rendering HIV resistant to cell-mediated destruction responses. In mature HIV-1 particles a conical-shaped capsid core encloses the viral RNA genome. Previous structural analysis of two- and three-dimensional arrays provided a molecular model of the capsid protein (CA) hexamer and revealed three interfaces in the lattice. Using the high-resolution NMR structure of the CA C-terminal domain (CTD) dimer and in particular the unique interface identified, it was possible to reconstruct a model for a tubular assembly of CA protein that fit extremely well into the cryoEM density map. A novel CTD-CTD interface at the local three-fold axis in the cryoEM map was confirmed by mutagenesis to be essential for function. More recently, the cryo-EM structure of the tube was solved at 8Å resolution and this cryo-EM structure allowed unambiguous modeling and refinement by large-scale molecular dynamics (MD) simulation, resulting in all-atom models for the hexamer-of-hexamer and pentamer-of-hexamer elements of spheroidal capsids. Furthermore, the 3D structure of a native HIV-1 core was determined by cryo-electron tomography (Cryo-ET), which in combination with MD simulations permitted the construction of a realistic all-atom model for the entire capsid, based on the 3D authentic core structure.
About Angela M. Gronenborn
Dr. Gronenborn received her Diploma (1975) and Doctoral (1978) degrees in Chemistry from the University of Cologne, Germany. After post-doctoral work with Jim Feeney at The National Institute for Medical Research in Mill Hill, London, UK she continued her research at NIMR in the Division of Physical Biochemistry. In 1984 she moved to the Max Planck Institute of Biochemistry in Martinsried (Munich) as head of the biological NMR group. In 1988 she relocated to the Laboratory of Chemical Physics in NIDDK at the National Institutes of Health in Bethesda, where together with Bax and Clore she was instrumental in developing NMR methodologies for biological macromolecules. Since 2005 she is a Professor at the University of Pittsburgh Medical School where she currently holds the UPMC Rosalind Franklin Chair in Structural Biology and, in 2011, was named Distinguished Professor of Structural Biology. She was elected to the National Academy of Sciences and the Norwegian Academy of Science and Letters in 2007 and 2010 respectively. In 2014, she received the Life Science Award from the Carnegie Science Center and was also elected to the Germany Academy of Sciences, Leopoldina.
Key contributions include the development of restrained molecular dynamics/simulated annealing algorithms and multidimensional, heteronuclear spectroscopic methods, which allowed the extension of conventional NMR methods to higher molecular weight systems. Dr. Gronenborn has solved solution structures of a large number of medically and biologically important proteins, including cytokines and chemokines, transcription factors and their complexes and various HIV and AIDS related proteins. Her extensive bibliography contains more than 470 articles and numerous book chapters.
Gronenborn AM, Birdsall B, Hyde EI, Roberts GCK, Feeney J, Burgen ASV. Direct observation by NMR of two coexisting conformations of an enzyme-ligand complex in solution. Nature 230, 273 (1980).
Oschkinat H, Griesinger C, Kraulis PJ, Sørensen OW, Ernst RR, Gronenborn AM, Clore GM. Three-dimensional NMR spectroscopy of a protein in solution. Nature 332, 374 (1988).
Clore GM, Gronenborn AM. Structures of larger proteins in solution: three- and four-dimensional heteronuclear NMR spectroscopy. Science 252, 1390 (1991).
Omichinski JG, Clore GM, Schaad O, Felsenfeld G, Traino, C, Appella E, Stahl SJ, Gronenborn AM. NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1. Science 261, 438-446 (1993).
Frank MK, Dyda F, Dobrodumov A, Gronenborn AM. Core mutations switch monomeric protein GB1 into an intertwined tetramer. Nat. Struct. Biol., 9(11): 877-885 (2002).
Byeon, IL, Meng X, Jung J, Zhao G, Yang R, Ahn J, Shi J, Concel J, Aiken C, Zhang P, Gronenborn AM. Structural convergence between Cryo-EM and NMR reveals intersubunit interactions critical for HIV-1 capsid function. Cell 139, 780 (2009). PMC2782912
Zhao G, Perilla JR, Yufenyuy EL, Meng X, Chen B, Ning J, Ahn J, Gronenborn AM, Schulten K, Aiken C, Zhang P. Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Nature 497, 643 (2013). PMC3729984
The endowed lecture series was established by David’s family, just one of many ways in which people have helped make a difference in advancing UC Davis’s commitments to teaching, research, and public service.
- 2016: Professor Sir Tom Blundell, Biochemistry, University of Cambridge. Biophysics, Computational Biology and the Discovery of New Medicines: The Emergence of Resistance in Cancer and Tuberculosis. (video)
- 2015: Professor Stephen Quake, School of Engineering, Stanford University and Howard Hughes Medical Institute. Single Cell Genomics. (video)
- 2014: Professor Arup Chakraborty, Laboratory for Computational Immunology, Massachusetts Institute of Technology. How to Hit HIV Where It Hurts.
- 2013: Professor Joanna Aizenberg, Harvard University, School of Engineering and Applied Science. Novel Biomimetic ‘Spiny’ Surfaces in Medical Applications.
- 2012: Professor Cheryl Arrowsmith, Structure Genomic Consortium, Department of Medical Biophysics, University of Toronto. Structural and Chemical Biology of Epigenetic Regulators.
- 2011: Professor John Kuriyan, Chancellor’s Professor, Department of Molecular and Cell Biology and Department of Chemistry, University of California, Berkeley. Molecular Mechanisms in Signal Transduction by Tyrosine Kinases.
- 2010: Professor Susan Lindquist, Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute, Broad Institute of MIT and Harvard Department of Biology, MIT. Protein Folding Driving the Evolution of Genomes.
- 2009: Professor Gregory Petsko, Gyula and Katica Tauber Professor, Department of Biochemistry and Chemistry, Brandeis University, Adjunct Professor, Department of Neurology and Center for Neurological Diseases, Harvard Medical School. Structural Neurology: Understanding, Treating and Preventing Neurodegenerative Diseases.
- 2008: Professor Christopher Dobson, John Humphrey Plummer Professor of Chemical and Structural Biology, Master of St. Johns College, Cambridge University, United Kingdom. Life on the Edge: The Nature and Origins of Protein Misfolding Diseases.
- Invited guest speaker, Professor Rohit Pappu, Washington University, A Student’s Remembrance of David Weaver.
- 2007: Professor Martin Karplus, Laboratoire de Chimie Biophysique, ISIS, Universite Louis Pasteur and Department of Chemistry and Chemical Biology, Harvard University, 2013 Nobel Prize in Chemistry, How Proteins Work: Insights from Simulations.
- Opening remarks by Dirk Laukien, Ph.D., Senior Scientific Fellow, Bruker Optics, Unfolding David Weaver’s Contributions at Bruker Optics.