Protein is matter of dual nature. As a physical object, a protein molecule is a folded chain of amino acids with diverse biochemistry. But it is also a point along an evolutionary trajectory determined by the function performed by the protein within a hierarchy of interwoven interaction networks of the cell, the organism, and the population. A physical theory of proteins therefore needs to unify both aspects, the biophysical and the evolutionary. Specifically, it should provide a model of how the DNA gene is mapped into the functional phenotype of the protein. Several physical approaches to the protein problem are reviewed, focusing on a mechanical framework which treats proteins as evolvable condensed matter: Mutations introduce localized perturbations in the gene, which are translated to localized perturbations in the protein matter. A natural tool to examine how mutations shape the phenotype are Green’s functions. They map the evolutionary linkage among mutations in the gene (termed epistasis) to cooperative physical interactions among the amino acids in the protein. The mechanistic view can be applied to examine basic questions of protein evolution and design.

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专题讨论会：蛋白质：无定形演化物质的物理学

蛋白质是双重性质的。作为物理对象，蛋白质分子是具有多种生物化学作用的氨基酸折叠链。但这也是沿着进化轨迹的一个点，该轨迹由蛋白质在细胞，生物体和种群的交织相互作用网络的层次结构中所执行的功能决定。因此，蛋白质的物理理论需要统一生物物理和进化两个方面。具体来说，它应该提供一个模型，说明如何将DNA基因映射到蛋白质的功能表型中。对蛋白质问题的几种物理方法进行了综述，重点关注将蛋白质视为可进化的凝聚物的机械框架：突变在基因中引入了局部扰动，这些扰动被翻译为蛋白质物质中的局部扰动。检验突变如何影响表型的自然工具是格林的功能。他们将基因突变（称为上位性）之间的进化连锁关系映射到蛋白质中氨基酸之间的协同物理相互作用。该机制的观点可以用于检查蛋白质进化和设计的基本问题。