Proteins exhibit structural variations due to thermal noise (dynamics) and genetic mutations (evolution). Using extensive protein structure databases, it is observed that native-state dynamics of proteins exhibit long-range correlations, resembling critical points in physical systems, which contribute to significant conformational changes like allosteric regulation. Additionally, data-driven analysis revealed correspondences between protein dynamics and evolution, shedding light on the robustness-plasticity tradeoff of proteins. Furthermore, based on AlphaFold structure predictions, the statistical trends in protein evolution were observed, highlighted by evolutionary dimensionality reduction. These findings underscore the universal principles of biocomplexity and may lead to advancements of protein engineering technologies.

Data science techniques can be used for “molecular archeology”. The ancestral gene/protein sequences are statistically deduced from a molecular phylogeny, and they are further used to resurrect the ancient molecules for laboratory experiments to elucidate their properties and structures. In this review, the researches, which applied this method for analyzing deep sea diving re-adaptation of whales or seals via the evolution of myoglobins, are described.

Importance of water in stabilizing the folded structure of proteins has long been well known thermodynamically. However, the understanding of the hydration water in protein stabilization at the microscopic molecular level has been insufficient. We have investigated the mobility of water around proteins by terahertz spectroscopy, comparing it with the thermodynamics and hydrogen bonding structure, and have revealed that “weakly affected water” by the protein is deeply involved in the stabilization of the folded structure. We have also shown that small organic molecules (osmolytes) indirectly contribute to protein stabilization/destabilization by changing the state of water.