Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session II

89-POS Board 42 Discovering Allosteric Communication Pathways on the Bacterial Ribosome: from Decoding Center to Peptidyl Transferase Center Pelin Uzun , Ozge Kurkcuoglu-Levitas. Istanbul Technical University, Istanbul, Turkey. Ribosome, a molecular machine synthesizing proteins in the cell, is mainly composed of small and large subunits (called 30S and 50S in bacteria) connected by multiple intersubunit bridges. Elucidating the communication pathways responsible for information transport among distant functional sites on the subunits is critical both to understand the functional mechanisms of the complex and to develop new antibacterial therapeutics targeting the ribosome. Various studies indicate sophisticated allosteric communication mechanisms between numerous functional sites of the complex carefully employed during the translation process, such as between the decoding center (DC), which is responsible for decoding genetic code on 30S, and the peptidyl transferase center (PTC), which mediates the peptide bond synthesis on 50S 1 . In this study, three different crystal ribosome structures of Thermus Thermophilus are investigated to obtain twenty shortest signaling pathways between DC (residue A1492) and PTC (residues A2451 and G2251). For this purpose, k-shortest path algorithm 2 is used with the elastic network approach 3 , describing the ribosome structure as a network of nodes linked by edges. Nodes are placed at alpha-carbon and phosphor atoms of residues, and length of edges between neighboring node-pairs are calculated based on atom-atom interactions. Results indicate that major and minor signaling paths exist between DC and PTC. These paths are composed of highly conserved and/or antibiotic binding residues, and pass through the B3 intersubunit bridge. Results suggest that B3 bear a critical position in signal transmission between DC and PTC, and give hints on new druggable sites in bacterial ribosome. 1) Rakauskaite, R; Dinman, J.D. Nucleic Acids Research, 2008, 36(5), 1497. 2) Yen, J. Y. Management Science, 1971, 17, 712. 3) Kurkcuoglu, O.; Turgut, O. T.; Cansu, S.; Jernigan, R. L.; Doruker, P. Biophysical Journal, 2009, 97, 1178.

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