Out-of-Equilibrium Biophysical Chemistry: The Case for Multidimensional, Integrated Single-Molecule Approaches

• DOI: 10.1021/acs.jpcb.1c02424
• Publication Date: 2021-09-10T17:33:10Z
• Authors: Narendar Kolimi; Ashok Pabbathi; Nabanita Saikia; Feng Ding; Hugo Sanabria; Joshua Alper
• Keywords: Biomolecule; Conformational ensembles

Out-of-equilibrium processes are ubiquitous across living organisms and all structural hierarchies of life. At the molecular scale, out-of-equilibrium (for example, enzyme catalysis, gene regulation, motor protein functions) cause biological macromolecules to sample an ensemble conformations over a wide range time scales. Quantifying conceptualizing structure–dynamics function relationship is challenging because continuously evolving multidimensional energy landscapes necessary describe nonequilibrium in macromolecules. In this perspective, we explore challenges associated with state-of-the-art experimental techniques understanding macromolecular function. We argue that it revisit how probe model functional biomolecular dynamics. suggest developing integrated single-molecule multiparametric force–fluorescence instruments using advanced dynamics simulations study biomolecules will provide path towards principles mechanisms behind paradigm