Physical and molecular bases of protein thermal stability and cold adaptation

[Display omitted] •No unique mechanism for thermal and cold stability and for thermal and cold functional adaptation.•Amino acid interaction and repulsion strengths depend on the temperature and on the protein context.•The stabilizing effect and functional role of protein structural and dynamical features vary with temperature.•Protein oligomerization and ligand binding influence thermal properties.•Understanding stabilization/adaptation mechanisms requires considering interaction and feature networks. The molecular bases of thermal and cold stability and adaptation, which allow proteins to remain folded and functional in the temperature ranges in which their host organisms live and grow, are still only partially elucidated. Indeed, both experimental and computational studies fail to yield a fully precise and global physical picture, essentially because all effects are context-dependent and thus quite intricate to unravel. We present a snapshot of the current state of knowledge of this highly complex and challenging issue, whose resolution would enable large-scale rational protein design.