Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

Quantifying the energy landscapes of ribosome function through simulation

The breadth of information available on ribosome structure and dynamics makes it the ideal system for systematically investigating the physical-chemical properties that enable large-scale biological processes. Through the use of simplified models (40,000-150,000 atoms) and explicit-solvent simulations, we are identifying the balance between structural flexibility and energetics during large-scale conformational transitions. Relatively long explicit-solvent simulations of complete ribosomes (200 nanoseconds to 1.3 microseconds) and simulations of ribosomal components (cumulative sampling of ten microseconds) provide quantitative relationships between tRNA movement, large-scale rotary motions and the energetic barriers encountered during function. These studies implicate specific experimentally-accessible coordinates for describing the free-energy landscape of collective dynamics in the ribosome. Complementary to explicit-solvent calculations, all-atom simulations that employ simplified descriptions of the energetics allow us to determine the role of configurational entropy during large-scale transitions. Building on energy landscape principles, these calculations provide a theoretical foundation that quantitatively bridges experimental kinetics, single-molecule measurements, structural/mutational data and theoretical calculations. With this knowledge, it is now possible to interpret the findings from these unique approaches within a consistent framework, which is allowing a unified description of the dynamics to emerge.

This research has been supported by NSF CAREER Award MCB-1350312.

Paul C. Whitford

Department of Physics
Northeastern University
Boston, MA 02115

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