We discuss here physics and evolution of globular proteins with a focus on the basic units of their structure and function, closed loops and elementary functional loops. A starting point of the journey here is a prebiotic evolution, in which short linear peptides and corresponding RNA duplexes with traits determined by demands to survive and to move on in the harshness of the Origin of Life emerged first. Next, we follow the fate of ring-like peptides, which apparently were the "Dayhoff fragments" that passed through abiogenic transition, formed first functional domains followed by their inclusion in multidomain structures, formation of complexes, assemblies, and molecular machines in later stages. I argue that physics, specifically polymer nature of protein chains, not only served as a determinant of the basic units of proteins-closed loops but also could play a decisive role in determining the size of another important structural unit-domain-based on the polymer nature of nucleic acids that governed the optimal ring closure size of DNA molecules. The protein closed loops served as scaffold for carrying elementary functions-descendants of ancient ring-like peptides, combinations of which provided the modern protein function universe. Another alliance between physics and evolution discussed here is the allosteric regulation of protein function, which is based on the structural dynamics underlying the allosteric signal transduction and its regulatory role. While the physics drive the structure-based conserved patterns of allosteric signalling determined by the folds, the evolution brings in a sequence diversity, allowing to alternate the allosteric communication and to make it archetypal for distinct functional (super)families using the same fold as the structural platform. Considering only few above aspects, I show that important lessons from the hand-in-hand walk of physics and evolution already helped to achieve the current state-of-the-art in understanding of protein structure and function. I conclude, however, that there is still even more to learn from Nature about long and remaining mainly mysterious 3.5 billion years endeavor.
Igor N. Berezovsky (Thu,) studied this question.