לוח שנה משולב

The ribosome is a complex molecular machine that, in order to synthesize proteins, has to decode mRNAs by pairing their codons with matching tRNAs. Decoding is a major determinant of fitness and requires accurate and fast selection of correct tRNAs among many similar competitors. However, it is unclear whether the present ribosome, and in particular its large deformations during decoding, are the outcome of adaptation to its task as a decoder or the result of other constraints. We derive the energy landscape that provides optimal discrimination between competing substrates and thereby optimal tRNA decoding. We show that the measured landscape of the prokaryotic ribosome is indeed sculpted in this way. This suggests that conformational changes of the ribosome and tRNA during decoding are means to obtain an optimal decoder. Our analysis puts forward a generic mechanism that may be utilized by other ribosomes and molecular recognition systems.

DNA origami, a powerful approach for molecular self assembly, enables the fabrication of molecular machines and robots from nucleic acids. We employed this method to construct nanorobots capable of manipulating the behavior of living cells, and exhibiting collective behaviors and swarm intelligence. However, how these machines and other structures fold without error and at high yields remains unknown. We are beginning to study how this process advances in time and space, to elucidate the entropic and mechanical constraints it operates within and enable the optimization of design and serial manufacturing for such machines in the future.

An emerging new direction of research focuses on developing ‘self-synthesizing materials’, those supramolecular structures that can promote their own formation by accelerating the synthesis of building blocks and/or an entire assembly. It was postulated recently that practical design of such systems can benefit from the ability to control the assembly of amphiphilic molecules into nano-structures. In this regard, we have studied extensively the replication of α-helix forming peptides that self-assemble to coiled-coil tertiary structures, and showed that such systems can self-organize into adaptive networks [1-3]. It has been postulated recently that shorter peptides with simpler sequences may serve as templates for self-replication, provided that they are able to arrange themselves into unique and well defined structures. I will thus further discuss the design, kinetic analysis and relevance to the origin of life of rather simple peptides, close analogs of the synthetic amphiphilic Glu-(Phe-Glu)n peptides that can form soluble one-dimensional β-sheet aggregates in water, and serve to significantly accelerate their ligation and self-replication [4-5].

[1] Dadon, Wagner, Ashkenasy "The Road to Non-enzymatic Molecular Networks", Angew. Chem. Int. Ed. 2008, 47, 6128-6136.
[2] Dadon, Samiappan, Yishay, Ashkenasy “Light-Induced Peptide Replication Controls Logic Operations in Small Networks” Chem. Eur. J. 2010 16, 12096-12099.
[3] Samiappan, Dadon, Ashkenasy “Replication NAND Gate with Light as Input and Output” Chem. Commun. 2011, 47, 710-712.
[4] Rubinov, Wagner, Rapaport, Ashkenasy "Self Replicating Amphiphilic β-Sheet Peptides" Angew. Chem. Int. Ed. 2009, 48, 6683-6686.
[5] Bourbo, Matmor, Shtelman, Rubinov, N. Ashkenasy, G. Ashkenasy “Self-assembly and Self-replication of Short Amphiphilic β-sheet Peptides” Origins. Life. Evol. Bios. 2011, 41, 563-567.

The aim of these lectures is to explain some remarkable recent results that are valid for systems far from equilibrium. These results, known as the Work Identities (Jarzynski, Crooks) and the Fluctuation Theorem (Cohen, Evans, Gallavotti and Morriss), quantify transient violations of the second principle. They rely on the fundamental time-reversal symmetry satisfied by most of the physical processes considered in statistical mechanics. During the last decade, these seminal results have been extended to various physical situations: we shall give a unified mathematical description of these generalizations and put a special emphasis on large deviation functions. These functions are expected to play, for systems out of equilibrium, a role akin to that of thermodynamic potentials. These concepts will be applied to simple systems such as the Brownian ratchet model for molecular motors and the asymmetric exclusion process.