Modeling energy-consuming biomolecular processes
Location: CECAM-HQ-EPFL, BCH2103, Lausanne, Switzerland
While historically cellular processes have been first modeled according to the laws of equilibrium thermodynamics, the cell is a non-equilibrium environment driven, and kept alive, by the consumption of a formidable quantity of energy: each day, the human body produces, and consumes, an amount of ATP close to its own mass. Understanding how energy consumption reshapes the energy landscape driving biomolecular dynamics and interactions, and possibly gives rise to novel and unexpected phenomena, is thus a crucial step for understanding the molecular basis of life.
Pioneering experimental and theoretical studies have shown that non-equilibrium physics is strictly required for correctly describing key cellular processes, including protein translation and DNA replication, whose remarkable fidelity had already been rationalized in the 1970s, and molecular motors walking on cytoskeletal filaments, a staple of biophysics in the 1990s and 2000s. More recently, a plethora of new non-equilibrium biomolecular phenomena have come under the scrutiny of the community. The ability of proteins to fold to their native states, which are typically assumed to correspond to equilibrium free-energy minima, is actually controlled in the cell by a host of ATP-driven co- and post-translational factors, including molecular chaperones, that can maintain proteins functional even under adverse conditions. Simple equilibrium polymer models cannot describe the cellular organization of DNA, which populates non-equilibrium ensembles controlled by Structural Maintenance of Chromosomes (SMC) proteins by means of their ATP consuming action[4-6]. Many bacterial cells use a complex dance of GTPase molecules that bind to and unbind from membranes to access dynamically unstable states, inaccessible in any equilibrium description, that spontaneously mark the position where cell division has to occur. Membranes are constantly deformed, pinched and excised by the concerted action of lipid kinases and phosphatases and by GTP- and ATP- consuming protein machines. Furthermore, biomolecular condensates, which are currently recognized as key players in cellular organization, are intimately regulated by energy-consuming enzymes and may display non-equilibrium, functional properties.
While experiments are providing ever more precise information about these fascinating processes, a renewed interest and new developments in non-equilibrium statistical physics have provided a new lens for their theoretical modeling. At the same time, efficient computational approaches have to be devised to face the technical challenges associated to the simulation of non-equilibrium cellular processes, which intimately rely on the interplay between biomolecular dynamics and enzymatic reactions [10-12].
The goal of this workshop is to bring together leading researchers to discuss recent experimental and theoretical progresses in the field, to identify key challenges and to foster further collaborations, with final aim of pushing the boundaries of current approaches and develop novel tools capable of providing a detailed yet comprehensive picture of non-equilibrium cellular functioning at the molecular scale.
Alessandro Barducci (Centre de Biologie Structurale (CNRS UMR5048, INSERM U1054)) - Organiser
Paolo De Los Rios (EPFL) - Organiser