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The Role of Theory in Biological Physics and...
Transcript of The Role of Theory in Biological Physics and...
The Role of Theory in Biological Physics and Materials:
A report to the National Science Foundation.
Chairs: Mike Thorpe, Arizona State UniversityAnders Carlsson, Washington University at St. Louis
Meeting held in Tempen 16 – 18 May 2004n 62 participants n Bruce Taggart, NSF
Daryl Hess, NSFDenise Caldwell, NSFKamal Shukla, NSF
Jiayin (Jerry) Li, NIGMS, NIHJohn Whitmarsh, NIH
Robert Eisenberg, APS Charles Day, Physics Today
Questionsn What are the important problems in biology that can
be solved with the help of theory?n What types of theory are most useful in treating
biological problems?n What new physics and materials science can be
learned by the study of biological systems?n What types of educational opportunities and
infrastructure support would be most helpful to nurture this community?
Outlinen Biomoleculesn Supramolecular Assembliesn Systems Biologyn Education and Infrastructure
Biomoleculesn Fundamental building blocks of living cellsn Their role is felt across the entire hierarchy of
biological ordern Physics has played a key role from the beginning in
developing our understanding of biomoleculesn Physically based theoretical methods are increasingly
used in biomolecular modeling
Protein Structure
The study of biomolecules was initiated with the double-stranded structure of DNA shown on the left and the original ball-and-stick model of myoglobin on the right the first 3D structure of a protein determined ( http://nobelprize.org/chemistry/laureates/1962/kendrew-lecture.pdf);
Cellular Mechanics and Molecular Motors
Schematic of thermal ratchets possibly related to molecular motors. The lateral bolts in frame (b) allow the ratchet to move to the right. [P. Nelson, “Biological Physics” (W. H. Freeman, New York, 2004), p. 414].
Bio-nano Devices
Snapshot of an MD simulation of water molecules in a carbon nanotube that is similar to diffusion of water in aquaporin[G. Hummer, J. C. Rasaiah, and J. P. Noworyta, Nature 414, 188 (2001)].
Protons Moving in Biomolecules
Molecular structure of the proton wire in gramicidin. [R. Pomes and B. Roux, Biophys. J. 82, 2304-2316 (2002)].
A molecular light switch made from oligopeptides [Yasutomi et al. Science 304, 1871, 1994 (2004)].
Interaction of Light with Biomolecules
Elastic Properties and Strain
The ribosome where proteins are assembled using instructions from the genetic code is one of the largest structures ever determined by X-ray crystallography. [J.H.Cate, M.M Yusupov, G.Z. Yusupova, T.N. Earnest, H.F Noller, Science 1999;285:2095-104.]
Challenges in Biomolecules
n Non-equilibrium statistical mechanics of small systems
n Improved molecular force fieldsn Multiscale approaches
Supramolecular Assembliesn Assembly and function of supramolecular structures
is crucial many functions - the cytoskeleton which determines cell shape and movement, lipid bilayers which demarcate the cell and its compartments, and multi-component assemblies forming complex machines
n Progress in understanding supramolecular assembly requires tools of biology, chemistry, physics, mathematics, and materials science
n Theory is crucial because probing the dynamics of function, assembly, and disassembly is difficult
Electrostatics of Macro-ions in Aqueous Solution
Complexes of DNA with multivalent cations at different concentrations of C+ and with proteins at different mono-valent salt concentrations. The electron micrograph is of Lambda bacteriophage genome condensed by multivalent particles [courtesy of J.-L. Sikorav, CEA-SACLAY, France].
Intracellular Networks of Semi-flexible Polymers
Schematic of a semi-flexible polymer showing “wiggles” produced by thermal fluctuations. The external force τ increases the length R of the polymer by pulling out the wiggles. [Courtesy of F. C. MacKintosh]
Biomembranes and Biopolymer Materials
Proposed raft structure with anchored proteins [R. G. W. Anderson and K. Jacobson, Science 296, 1821 (2002)]
Self-assembly of Tobacco Mosaic Virus from solution of capsid proteinplus RNA molecules [H. Fraenkelconrat and R. C. Williams, Proc. Nat. Acad. Sci. 41, 690 (1955)].
Rod-Like Virus
Viral Capsids
DNA ejection from Bacteriophage T5 [courtesy of M. de Frutos, L. Letellier, and E. Raspaud, Orsay, France (2004)]
Chromatin Structure
Chromatin structure [P. Ridgway, C. Maison, and G. Almouzni, Atlas Genet. Cytogenet. Oncol. Haematol. (May 2002)
http://www.infobiogen.fr/services/chromcancer/Deep/ChromatinDeep.html
Aggregation of Mis-folded Proteins
Autocatalysis of the prion protein (normal-PrPc, infectious-PrPSc) at the monomer level (upper picture) or via aggregation (lower).[Courtesy of D. L. Cox].
Amyloid plaque from the human prion disease Kuru [from feany-lab.bwh.harvard.edu/link2/]
The Perutz zipper [C.A. Ross et al,Proc. Natl. Acad Sciences 100 (2003)
Precision Self-assembly of Organelles
Origin of the helical shape of a flagellar filament [K. Namba and F. Vonderviszt, Quart. Rev. Biophys. 30, 1 (1997)].
Synthesis of New Materials Using Cellular Machinery
Challenges inSupramolecular Assembliesn Theories need to be developed at length and time
scales appropriate for comparison with experimentn Theory is especially useful in developing general
pictures, ideas, and concepts.n Methods are needed for dealing with nonequilibrium
problemsn Key overriding question: what factors determine the
dynamics and perfection of self-assembly?
Systems Biologyn The ultimate many-body problem of living mattern How does function emerge from interaction of
numerous molecular components?n Ranges from cell level to organismic and higher levels
Life’s Complexity Pyramid
[Z. N. Oltvai and A.-L. Barabási, Science 298, 763 (2002)].
Signal Transduction Network
Bacterial Chemotactic System.
Gene Regulatory Network
[U.S. Department of Energy Genomics: GTL Program, http://www.ornl.gov/sci/techresources/Human_Genome/graphics/slides/sciregulatory.shtml.]
Evolution: Phylogentics, Comparative Genomics, and Network Evolution
The DNA packaged in the chromosomes contains the genes that encode for proteins.
Challenges in Systems Biologyn Understanding specificity, robustness, and
evolvabilityn Develop methods for evaluating and studying
modularity of biological systemsn Physics can guide biology in focusing study on a
small number of key degrees of freedom
Overriding Scientific Themesn Non-equilibrium thermodynamics. Almost all
biological phenomena are inherently non-equilibrium, but most condensed-matter and materials theory has focused on equilibrium problems. Study of biology and biological materials could aid development of conceptual structures for non-equilibrium phenomena.
n Self-assembly. Seen on an enormous range of length scales, and is often highly accurate. Self-assembling materials may well be a major thrust in future materials development.
Education and Infrastructuren Biological physics is expanding very rapidlyn Existing efforts, such as graduate training programs
and summer schools, point the way to more comprehensive efforts.
Community-Building
n Bring physicists and biologists together. n Define important problems of common interest for
biologists and physicistsn Provide a forum and environment to nuture
innovative new approaches to biology that address the fundamental issues of living matter
n Establish interdisciplinary (and theory/experiment) collaboration
n Provide education in biological problems for graduate, postdoctoral and more senior level physics researchers, and education in quantitative methods and physics approaches for biologists.
Recommendationsn The expansion of NSF joint funding linking the NSF,
especially DMR, with the NIH. n The establishment of regional research and training
centers in biological physics and materials to bring together biologists and physicists.
n The expansion of postdoctoral fellowships supporting transitions into biological physics.
n The development of more summer schools, internet resources and textbooks.
n Support for sabbatical visits to institutions with active biological physics and/or biology programs.
Recommendations
n Undergraduate and graduate courses contain more examples of physics being used in biology and vice versa.
n Encourage more flexibility in graduate programs, especially in qualifying procedures in masters and doctoral programs.
Report
n biophysics.asu.edu/workshop/report.html
n Thanks for your attention!