Enzymes spin the wheel of life by catalyzing a myriad of chemical reactions central to the growth, development, and metabolism of all living organisms. Without enzymes, essential processes would progress so slowly that life would virtually grind to a halt, and the quest to determine their inner workings thus continues to attract and fascinate scientists over a broad range of disciplines. Cutting-edge methods now allow one to observe and manipulate individual enzymes, as well as other molecules, in their reaction course. These revealed that chemistry at the single-molecule level is inherently stochastic and, at times, extremely unintuitive. Thermal fluctuations push molecules to vibrate erratically and force a probabilistic description, but classical approaches are deeply entrenched in determinism, and so is our basic expectation for how things should behave in the world around us. The main objective of this project is to bring advanced theoretical methods and mathematical tools to the analysis of stochastic fluctuations, of enzymes and other molecules, at the single-molecule level. These will be based on state-of-the-art approaches in statistical physics and stochastic processes that we will adapt and further advance to need. Equipped with mathematical techniques that have so far been foreign to the field, we expect to rectify fundamental flaws in our understanding, predict the emergence of novel phenomena, and develop novel inference methods for physically meaningful parameters that have so far evaded direct measurement. The amalgamation of all these efforts will pave the way to large-scale, multi-tier, characterization of stochastic fluctuations which is expected to transform our understanding of chemical kinetics at the single molecule level.
