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.

通常，蛋白质会折叠成组织良好的三维结构以发挥作用。这种功能形状的稳定性可能会受到外部环境条件的干扰，例如温度。了解蛋白质抵抗热应力的分子因素具有重要意义。首先，它可以帮助设计能够在高温条件下进行有效催化的热稳定性酶。其次，它是破译地球上生命适应的进化途径所需的重要知识积木。由于原子模拟和临时增强采样技术的发展，现在可以在计算机上研究这个问题，从而为实验提供支持。在描述了方法方面之后，本章建议对两个问题进行扩展讨论。首先，我们专注于嗜热蛋白，这是解决热稳定性和分子进化问题的完美模型。其次，我们讨论了蛋白质热稳定性如何受到拥挤的类似体内条件的影响的问题。