Caswell Benjamin T, Summers Thomas J, Licup Gerra L, Cantu David C
Department of Chemical and Materials Engineering, University of Nevada, Reno, Reno, Nevada 89557, United States.
ACS Omega. 2023 Jun 28;8(27):24302-24310. doi: 10.1021/acsomega.3c01473. eCollection 2023 Jul 11.
The mutation space of spatially conserved (MSSC) amino acid residues is a protein structural quantity developed and described in this work. The MSSC quantifies how many mutations and which different mutations, i.e., the mutation space, occur in each amino acid site in a protein. The MSSC calculates the mutation space of amino acids in a target protein from the spatially conserved residues in a group of multiple protein structures. Spatially conserved amino acid residues are identified based on their relative positions in the protein structure. The MSSC examines each residue in a target protein, compares it to the residues present in the same relative position in other protein structures, and uses physicochemical criteria of mutations found in each conserved spatial site to quantify the mutation space of each amino acid in the target protein. The MSSC is analogous to scoring each site in a multiple sequence alignment but in three-dimensional space considering the spatial location of residues instead of solely the order in which they appear in a protein sequence. MSSC analysis was performed on example cases, and it reproduces the well-known observation that, regardless of secondary structure, solvent-exposed residues are more likely to be mutated than internal ones. The MSSC code is available on GitHub: "https://github.com/Cantu-Research-Group/Mutation_Space".
空间保守（MSSC）氨基酸残基的突变空间是在本研究中开发并描述的一种蛋白质结构量。MSSC量化了蛋白质中每个氨基酸位点发生了多少种突变以及哪些不同的突变，即突变空间。MSSC根据一组多个蛋白质结构中的空间保守残基来计算目标蛋白质中氨基酸的突变空间。空间保守氨基酸残基是根据它们在蛋白质结构中的相对位置来确定的。MSSC检查目标蛋白质中的每个残基，将其与其他蛋白质结构中相同相对位置的残基进行比较，并使用在每个保守空间位点发现的突变的物理化学标准来量化目标蛋白质中每个氨基酸的突变空间。MSSC类似于对多序列比对中的每个位点进行评分，但它是在三维空间中考虑残基的空间位置，而不仅仅是它们在蛋白质序列中出现的顺序。对示例案例进行了MSSC分析，它再现了一个众所周知的观察结果，即无论二级结构如何，溶剂暴露的残基比内部残基更容易发生突变。MSSC代码可在GitHub上获取：“https://github.com/Cantu-Research-Group/Mutation_Space”。
