Mutation Space of Spatially Conserved Amino Acid Sites in Proteins

[Image: see text] 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”.