Nonequilibrium free energy transduction in biomolecular machines

点击翻译按钮获取中文摘要

Background I develop fundamental statistical physics to understand how living things address their operational molecular-scale imperatives: performing productive functions (including efficient energy transduction) rapidly while driven by strong mechanical and chemical forces, using nanoscale soft-matter objects. My long-term goal is to elucidate the physical limits-given these daunting biophysical challenges-on the efficiency, precision, speed, robustness, and tunability of molecular energy-transduction machinery; the trade-offs among these desirable characteristics; the designs of molecular machines that achieve these limits; and the extent to which naturally evolved systems conform to these predictions. Short-Term Objectives In the next five years, my research will focus on three Aims, two that use theory to understand the physics of biomolecular machines and a third that applies our theoretical framework to collaborative laboratory experiments: Uncover design principles for mechanical transduction of chemical free energy. We will develop basic theoretical frameworks and perform numerical simulations of model machines to understand nonequilibrium energy flows in intricately coupled systems, thereby uncovering design principles for energy transduction by proteins, the complex mechanical objects that drive biology. Develop theoretical frameworks for heterogeneous multi-stage energy transduction. We will derive theory and numerically explore energy flows through complex machines with many components, to understand how they achieve directionality and ensure robust operation despite strong fluctuations and many opportunities for energy leakage. Design, analyze, and interpret experiments probing molecular energy transduction. In collaborative experiments, we will test our new theories' utility in model biophysical systems and core molecular machines, to understand how energy can be saved by `smart' operation, and how much naturally evolved machines are tuned to improve energetic efficiency and other functionality. Impact My research program (providing training for many young scientists and instilling valuable quantitative skills for the modern workforce) develops basic theory and demonstrates its utility in experiments on molecular machines, thereby producing fundamental and practical breakthroughs in this emerging interdisciplinary field. Identifying governing physical constraints will help uncover the basic design principles underlying functional driven energy transduction in biology, in turn illuminating the (constrained) evolutionary optimization of molecular machines and improving our understanding of the physical underpinnings of life. These findings will provide quantitative guidance for improving functionality in novel synthetic machines, with potential technological applications to bolster Canadian industry, including enhanced efficiency in artificial photosynthetic materials and computer memory.