text: Phosphomimetics are amino acid substitutions that mimic a phosphorylated protein, thereby activating (or deactivating) the protein. Within cells, proteins are commonly modified at serine, tyrosine and threonine amino acids by adding a phosphate group. Phosphorylation is a common mode of activating or deactivating a protein as a form of regulation. However some non-phosphorylated amino acids appear chemically similar to phosphorylated amino acids. Therefore, by replacing an amino acid, the protein may maintain a higher level of activity. For example, aspartic acid can be considered chemically similar to phospho-serine, due to it also carrying a negative charge. Therefore, when an aspartic acid replaces a serine, it is a phosphomimetic of phospho-serine and can imitate the protein always in its phosphorylated form. However, differences in between the phosphomimetics compound and the phosphorylated residue, notably differences in ramachandran distributions, charge states and size, can alter the protein sufficiently to result in significant differences in behavior. Phosphonate-based compounds have been used as phosphotyrosine analogues, as they are less enzyme labile and are physiologically more stable.