Geconserveerde bindingsplaatsen

Generally, ligand binding sites are located within specific amino acid clusters or domains, dedicated to a certain type of interaction.  

Parts that are crucial to the function of a domain, such as ligand binding, remain unchanged during evolution because, as a rule, mutations that eliminate vital functions are eliminated by natural selection. 

For instance, many nuclear proteins, including transcription factors, contain FF domains that bind to RNA polymerase II. These domains get their name from the two phenylalanine amino acids they contain on separate helices. 

These phenylalanine amino acids, together with a few other highly-conserved amino acids form the hydrophobic core of the binding site.

Replacing these amino acids would disrupt the formation of this specific structure, hence affect its ability to bind to RNA polymerase II. 

Scientists use evolutionary tracing to find conserved regions of domains. This is performed by comparing genome and protein sequences of similar domains and identifying the amino acids that remain unchanged.

Subsequent analyses of these related sequences allow identification of clusters formed by the conserved amino acids. These data can be used to create 3D models to determine the shapes of proteins as well as the optimal structures of their binding sites.

Analyzing conserved sequences and structures helps scientists understand evolutionary relationships between proteins but also allows them to predict binding sites of novel proteins containing comparable clusters.