Protein thermal stability.

Proteins, in general, fold to a well-organized three-dimensional structure in order to function. The stability of this functional shape can be perturbed by external environmental conditions, such as temperature. Understanding the molecular factors underlying the resistance of proteins to the thermal stress has important consequences. First of all, it can aid the design of thermostable enzymes able to perform efficient catalysis in the high-temperature regime. Second, it is an essential brick of knowledge required to decipher the evolutionary pathways of life adaptation on Earth. Thanks to the development of atomistic simulations and ad hoc enhanced sampling techniques, it is now possible to investigate this problem in silico, and therefore provide support to experiments. After having described the methodological aspects, the chapter proposes an extended discussion on two problems. First, we focus on thermophilic proteins, a perfect model to address the issue of thermal stability and molecular evolution. Second, we discuss the issue of how protein thermal stability is affected by crowded in vivo-like conditions.