## 1 From the Structure-Function Paradigm to Structure-Motion-Function  
Over 60 years ago, [PERSON]'s postulate that \"the native secondary and tertiary structures are contained in the amino acid sequence itself\" [1] laid out the foundations of the central dogma of structural biology, i.e., that the sequence of a protein contains the information required to adopt a defined 3D-structure and, hence, function (see historical overview in [2]). This so-called structure-function paradigm was formulated during the time when biomolecular crystallography was flourishing. According to [PERSON], X-ray crystallography created \"the misconception... that the atoms in a protein are fixed in position\" [3]. This view is also shared by cryo-EM pioneer [PERSON], who wrote that \"the idea of \"a\" molecular structure has been largely created by X-ray crystallographic practice\" [4]. As a consequence, a static view of proteins, in which one sequence folds into a unique \"native conformation\" responsible for function, became prevalent. Nevertheless, an alternative, dynamic view of proteins as an ensemble of conformations, more akin to the principles of physics, had been proposed long before by [PERSON], [PERSON], and others in the 1930s [5]. Fast forward in time to our days, and this early dynamic vision appears present. As our technology to capture proteins in action evolved (NMR, cryo-EM, etc.), it became clearer every day that proteins do not fold into a single static \"native\" structure, but are rather dynamic machines in continuous motion that explore complex and rugged energy landscapes [6], transitioning between multiple meta-stable minima. Such transitions encompass a wide hierarchy of time and length scales--from picosecond atomic fluctuations to microsecond or millisecond allosteric changes or breathing motions--and, importantly, are instrumental for proteins to sense and respond to environmental signals like ions or ligands [7; 8; 6].  
Protein motions not only mediate or execute biological work--channel gating, ion pumping, transport, etc.--but also reshape interactions with other partners. Therefore, they are central for molecular recognition [9; 10; 11], no matter whether it involves conformational selection or induced fit [12; 13]. Even eminently local processes such as enzyme catalysis can involve dynamic changes such as side chain fluctuations or the unfolding of binding sites [14; 15; 16]. For intrinsically disordered proteins, flexibility is so extreme that the classical concept of a discrete number of well-defined native 3D shapes or conformers becomes almost meaningless; they can only be statistically described as ensembles of interconverting conformations [17; 18]. Nevertheless, a majority of proteins fall in the middle ground between perfect rigidity and chaotic disorder, a boundary where discrete rigid domains or subunits exquisitely rearrange in response to signals. Cooperative motions, allosteric propagation, and large-scale conformational changes spontaneously emerge from this frontier of harnessed flexibility to create function, as pioneering work by [PERSON] showed [16].  
Back in 1987, [PERSON] and [PERSON] first noted the similarity of MD fluctuations with evolutionary changes across the globin family [19], inauguring a fruitful line of evolutionary and structural dynamics comparisons to this day. Since then, structural data have grown exponentially, and Elastic Network Models (ENMs) [20; 21; 22; 23] have revealed that such fluctuations are largely defined by molecular shape and determine functional motions. Overall, this has led to a new structure-motion-function dogma, where molecular shape determines intrinsic motions, and motions make function, a concept increasingly supported via cryo-EM ensembles [24; 25]. Therefore, it is time to ask: if molecular motions mediate function, are they maybe a key object of evolutionary selection? Here, we briefly review evidence from structural biology and ENMs research, that points to shape-encoded motions as an essential matter for evolution.