Amino acids fulfil a diverse range of roles in proteins, each utilising its chemical properties in different ways in different contexts to create required functions. For example, cysteines form disulphide or hydrogen bonds in different circumstances and charged amino acids do not always make use of their charge. The repertoire of amino acid functions and the frequency at which they occur in proteins remains understudied. Measuring large numbers of mutational consequences, which can elucidate the role an amino acid plays, was prohibitively time consuming until recent developments in deep mutational scanning. In this study we gathered data from 28 deep mutational scanning studies, covering 6291 positions in 30 proteins, and used the consequences of mutation at each position to define a mutational landscape. We demonstrated rich relationships between this landscape and biophysical or evolutionary properties. Finally, we identified 100 functional amino acid subtypes with a data-driven clustering analysis and studied their features, including their frequencies and chemical properties such as tolerating polarity, hydrophobicity or being intolerant of charge or specific amino acids. The mutational landscape and amino acid subtypes provide a foundational catalogue of amino acid functional diversity, which will be refined as the number of studied protein positions increases.

中文翻译：

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在深层突变环境中探索氨基酸功能

氨基酸在蛋白质中扮演着各种各样的角色，每种氨基酸在不同的情况下以不同的方式利用其化学特性来创造所需的功能。例如，半胱氨酸在不同情况下形成二硫键或氢键，带电荷的氨基酸并不总是利用其电荷。氨基酸功能的组成及其在蛋白质中出现的频率仍未得到充分研究。测量大量突变结果（可以阐明氨基酸的作用）非常耗时，直到深度突变扫描的最新进展。在这项研究中，我们从28个深度突变扫描研究中收集了数据，涵盖30种蛋白质中的6291个位置，并使用每个位置处的突变结果来定义突变态势。我们证明了这种景观与生物物理或进化特性之间的丰富关系。最后，我们通过数据驱动的聚类分析确定了100个功能性氨基酸亚型，并研究了它们的特征，包括它们的频率和化学性质，例如耐受极性，疏水性或不耐受电荷或特定氨基酸。突变态势和氨基酸亚型提供了氨基酸功能多样性的基本目录，将随着所研究蛋白质位置数量的增加而完善。疏水性或不耐电荷或特定氨基酸。突变态势和氨基酸亚型提供了氨基酸功能多样性的基本目录，将随着所研究蛋白质位置数量的增加而完善。疏水性或不耐电荷或特定氨基酸。突变态势和氨基酸亚型提供了氨基酸功能多样性的基本目录，将随着所研究蛋白质位置数量的增加而完善。