Biomathematics Seminar: Listening to Noise in Biological Physics from Protein Dynamics to Evolutionary Landscapes
14 October 2008 14:15 in The Kingsley Barrett Lecture Theatre (CLC407)
We visit several examples of thermal noise and its analogies in molecular and evolutionary biology:
(1) we explore the mechanism of `allostery without conformational change'  by the use of coarse-grained statistical mechanical models of specific examples in molecular biology. Brownian motion excites internal degrees of freedom, which may then transmit information on state of binding to substrates across large protein domains. New examples of this important effect are continually coming to light at present as NMR and other techniques reveal dynamic, as well as structural, information on protein states. We treat the cases of the lac repressor , the coiled-coil dynein tubulin-binding stalk  and the met repressor , and build a model for recent remarkable experimental results on the CAP dimer 
(2) Brownian noise in single biomolecule AFM force spectroscopy can provide an additional window into dynamic processes occurring as the protein or polysaccharide unfolds .
(3) A beautiful mathematical analogy between a wide class of evolutionary models and statistical mechanics on an energy landscape motivates a multiscale model of genotype and phenotype that allows explicit accounting of genotype `entropy' and the `free fitness function'.
 A. Cooper and D.T. Dryden, `Allostery without conformational change. A plausible model.',Eur. Biophys. J. 11, 103-109 (1984).
 R.J. Hawkins and T.C.B. McLeish, `Coarse-Grained Model of Entropic Allostery', Phys. Rev. Letts, 93, 098104 (2004).
 R.J. Hawkins and T.C.B. McLeish, `Dynamic allostery of protein alpha helical coiled-coils', J. R. Soc. Interface, 3, 125-138 (2005).
 R. J. Hawkins and T. C. B. McLeish, `Coupling of Global and Local Vibrational Modes in Dynamic Allostery of Proteins', Biophys. J., 91, 2055-2062 (2006).
 N. Popovych, S. Sun, R. H. Ebright and C. G. Kalodimos, `Dynamically driven protein allostery', Nature Struct. Biol., 13, 831-838 (2006).
 B. S. Khatri, M. Kawakami, K. Byrne, D. A. Smith, and T. C. B. McLeish, `Entropy and Barrier-Controlled Fluctuations Determine Conformational Viscoelasticity of Single Biomolecules', Biophys. J., 92, 1825-1835 (2007).
 B.S. Khatri, T.C.B. McLeish and R. Sear, in preparation.