Seminar of the School of Physical Sciences
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Emergence of Mechanical Functionality of Proteins
Date: December 13, 2017 (Wednesday)
Abstract: Proteins are versatile bio-machines that perform all essential tasks in living organisms from immunity to structural support. Most of these activities require large scale motions of the protein. Recently it has been shown that floppy regions connecting distant sites of the protein are responsible for producing these motions [1, 2, 3]. We have used this idea to explore a fundamental question: how a given genetic sequence produces a functional protein? Using ideas from Condensed Matter Physics we have developed a microscopic model to study the evolution of a non-functional to functional protein [4]. A fitness parameter emerges naturally that describes the mechanical functionality of the protein. Our model enables us to quantify other fundamental quantities like epistasis as the mechanical interactions between two mutations. The model also provides a template for an explicit mapping from the genotype to phenotype of functional proteins. Other physical applications of this idea are also discussed.
[1] Mitchell MR, Tlusty T, Leibler S, Strain analysis of protein structures and low dimensionality of mechanical allosteric couplings, Proc Natl Acad Sci U S A 113(40):E5847–E5855 (2016).
[2] H. Qu and G. Zocchi, How enzymes work: A look through the perspective of molecular viscoelastic properties, Phys Rev X 3 (2013).
[3] Tsvi Tlusty, Albert Libchaber, and Jean-Pierre Eckmann, Physical model of the genotype-to-phenotype map of proteins, Phys Rev X (2017).
[4] Sandipan Dutta, J. P. Eckmann, Albert Libchaber, and Tsvi Tlusty, Green function of correlated genes and the mechanical evolution of protein, Proc Natl Acad Sci U S A (In Press).