Biophysical Society Thematic Meeting| Lima 2019

Revisiting the Central Dogma of Molecular Biology at the Single-Molecule Level

Sunday Speaker Abstracts

MECHANICAL FINGERPRINTS OF BIOMOLECULES, DECODED Olga K. Dudko 1 ; 1 University of California, San Diego, Department of Physics, La Jolla, CA, USA

The capacity of biological macromolecules to function as exceedingly sophisticated and efficient cellular machines – switches, assembly factors, pumps, or motors – is realized through their conformational transitions. Conformational transitions can be induced, monitored, and manipulated in single-molecule force experiments. The relationship between the applied force and molecular extension, which is revealed in these experiments, identifies a given biomolecule and thus serves as the molecule’s mechanical fingerprints. I will present a set of analytically tractable approaches to interpreting single-molecule force spectroscopy measurements in terms of kinetic rates, activation barriers, and pathways. On the fundamental side, being rooted in non- equilibrium statistical mechanics, these analytical approaches help reveal the unifying principles underneath the bewildering diversity of biomolecular behaviors. On the practical side, the analytical solutions that result from these approaches are well-suited for a direct fit to experimental data, yielding the key parameters that govern biological processes at the molecular level. USING A SYSTEM’S EQUILIBRIUM BEHAVIOR TO REDUCE ITS ENERGY DISSIPATION IN NON-EQUILIBRIUM PROCESSES Sara Tafoya 1,2 ; Steven Large 4 ; Shixin Liu 3 ; David Sivak 4 ; Carlos Bustamante 2,5 ; 1 LUMICKS USA, San Mateo, CA, USA 2 University of California, Berkeley, Physics, Chemistry and Molecular Biology, Berkeley, CA, USA 3 Rockefeller University, Biochemistry, Biophysics, Chemical Biology, and Structural Biology Genetics and Genomics , New York, NY, USA 4 Simon Fraser University, Department of Physics, Vancouver, BC, Canada 5 Howard Hughes Medical Institute, Berkeley, CA, USA Cells must operate far from equilibrium, utilizing and dissipating energy continuously to maintain their organization and to avoid stasis and death. However, they must also avoid unnecessary waste of energy. Recent studies have revealed that molecular machines are extremely efficient thermodynamically when compared to their macroscopic counterparts. However, the principles governing the efficient out-of-equilibrium operation of molecular machines remain a mystery. A theoretical framework has been recently formulated in which a generalized friction coefficient quantifies the energetic efficiency in non-equilibrium processes. Moreover, it posits that to minimize energy dissipation, external control should drive the system along the reaction coordinate with a speed inversely proportional to the square root of that friction coefficient. Here, we demonstrate the utility of this theory for designing and understanding energetically efficient non-equilibrium processes through the unfolding and folding of single DNA hairpins.

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