From static structures to dynamic energy landscapes: the latest revolution in molecular biology.

Abstract

Over a decade ago, in an Editorial, we proposed that beyond the foundational discovery of the DNA double helix, modern molecular biology has undergone a second revolution: a shift from static, single-structure models to dynamic, ensemble-based energy landscapes that define biomolecular function. Recently, Quarterly Reviews of Biophysics revisited this question, arguing that this shift is not merely conceptual but represents a revolution that explains functional regulation and enables the design of next-generation allosteric therapies. These ideas-driven by physics and chemistry-have transformed the landscape concept from a theoretical framework into the standard paradigm for biological mechanisms. Here, focusing on proteins, we discuss how the dynamic ensemble vision is reimagining molecular biology, using examples such as allosteric shifts in kinases and the discovery of cryptic pockets for drug design.