Bulletin of the American Physical Society
APS March Meeting 2019
Volume 64, Number 2
Monday–Friday, March 4–8, 2019; Boston, Massachusetts
Session L51: Delbruck Prize SymposiumInvited
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Sponsoring Units: DBIO Chair: William Bialek, Princeton University Room: BCEC 253A |
Wednesday, March 6, 2019 11:15AM - 11:51AM |
L51.00001: Max Delbruck Prize in Biological Physics Talk: The Physics of Cellular Proteostasis Invited Speaker: Ken Dill In order for cells to function, their proteins must be folded and not aggregated. This healthy state is maintained by a complex energy-expensive system of chaperones, and synthesis and degradation machinery. This is among the most central and complex `decision-making' processes of simple cells. We model proteostasis by combining the dynamics of the chaperone binding and trafficking with the kinetics of protein folding and aggregation. We also explore the rates of evolution of protein sequences and how the chaperones modulate those rates. |
Wednesday, March 6, 2019 11:51AM - 12:27PM |
L51.00002: Max Delbruck Prize in Biological Physics Talk: Exploring the Energy Landscape for Protein Folding and Function: Integrating Structural Models and Sequence Coevolution Information. Invited Speaker: Jose Onuchic Energy landscape theory and the funnel concept have been a powerful approach to study protein folding dynamics and function. The discovery that an accurate estimate of the joint probability distribution of amino acid occupancies in protein families provides insights about residue-residue coevolution and concrete details about protein folding landscapes has also advanced structural biophysics. Our realization that the collection of couplings and local fields as parameters of such distribution is inherently connected with the thermodynamics of sequence selection towards folding and function demonstrates the importance of coevolutionary methods to understand stability and function of biomolecules. The synergy between structure based models and coevolutionary information has spearheaded the field of structure prediction, including protein and RNA, as well as accelerating the discovery of functional structural states and the prediction of protein complexes. Coevolution signals can also be used to create protein recognition metrics, which led to successful experimental efforts, and the uncovering of novel molecular interactions. This idea has opened the door to encode recognition in protein pairs. Coevolved interfaces can also be combined with small molecule hot spot estimation methods to improve the discovery of druggable interfaces. Recently this approach has been used to predict extremely large protein assemblies consisting of structural maintenance of chromosomes (SMC) and kleisin subunits which are essential for the process of chromosome segregation across all domains of life. While limited structural data exist for the proteins that comprise the (SMC)–kleisin complex, using an integrative approach combining both crystallographic data and coevolutionary information, we have predicted an atomic-scale structure of the whole condensing complex in prokaryotes. |
Wednesday, March 6, 2019 12:27PM - 1:03PM |
L51.00003: Using evolutionary repair to learn about biological functions Invited Speaker: Andrew Murray Although many biological processes, such as DNA replication and chromosome segregation, are universal and many of the proteins that mediate them have persisted since the last common ancestor, other components have appeared and disappeared during evolution. We have removed important, but non-essential components from two different processes, DNA replication and chromosome segregation, allowed cells to accumulate mutations that restore reproductive fitness to nearly wild-type levels, and studied how these mutations affect DNA metabolism. In both cases, mutations alter multiple aspects of DNA metabolism with the effects of the different mutations being approximately additive and at least one of the adaptations is to slow an aspect of DNA replication. We discuss the trade-off between the speed of DNA replication and the accumulation of harmful intermediates in wild-type and mutant cells and how mutations can regulate the trade-off to improve reproductive fitness. |
Wednesday, March 6, 2019 1:03PM - 1:39PM |
L51.00004: Fitness Landscapes of Ribozymes Invited Speaker: Irene Chen Evolutionary outcomes are difficult, if not impossible, to predict, largely because the effect of any possible mutation is unknown. In other words, understanding evolution requires detailed knowledge of the relationship between sequence and activity, or the fitness landscape. Molecules explore the fitness landscape in sequence space during evolution, much as proteins explore the folding landscape in conformational space. Inspired by the RNA World theory of early life, in which RNA would carry information and also perform catalytic functions, we study the emergence and evolution of functional RNAs. Our experimental efforts focus on mapping complete fitness landscapes of ribozyme activity. We also study how confinement in a vesicle affects RNA activity and structure. These studies inform our understanding of the likelihood of emergence of function and the roles of chance vs. natural selection in prebiotic evolution. |
Wednesday, March 6, 2019 1:39PM - 2:15PM |
L51.00005: From Tunneling Pathways to Essential Biological Function Invited Speaker: David Beratan Energy capture, storage, and conversion in living systems relies, fundamentally, on the flow of electrons and protons. The transport of electrons through proteins uses cofactors, special chemical groups that sequester electrons as they hop among these sites thorugh otherwise insulating proteins. These cofactors trade electrons with one another via electron tunneling. Electrons thus move across membranes, generating a proton gradient, and leading to the synthesis of energy storing chemical bonds. Electron transfer reactions also participate in essential reaction of biosynthesis, damage repair, and signaling. Electrons flow in biology on time scales from picoseconds to seconds, and the trick for insuring that the electrons get to the right places at the right times is to employ electon tunneling pathways between the charge localizing cofactors. I will descibe the theoretical framework for describing how proteins control these reations with tunneling pathways, and will discuss research frontiers in that have become accessible to theoretical analysis as a consequence of the tunneling pathways framework. Examples will include the repair of DNA damage by the protein photolyase, the micrometer length scale flow of electrons through extracellular bacterial nanoweires that enable respiration in some aerobic bacteria (when deprived of oxygen) through the use of biotic-abiotic charge exchange (i.e., electron transfer to rocks), and electron bifurcation - a reaction that couples electron flow between two-electron donors and single-electron carriers. |
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