A pairwise coupling is a pattern between two covariant amino acids, and those couplings are conserved across evolution due to the functional and structural constraints. They can be used to predict protein structures, binding interfaces and protein-protein interactions, as well as protein design.

The couplings between pairwise amino acids are analyzed using the principles in the SAEC method¹ to make the residue communities as much statistically independent as possible. The principles are as follows:

• community I consists of residues at the \(i\)th position of \(\mathbf{v}_{k=2}^i>\text{max}(\mathbf{v}_{k=4}^i, \epsilon)\),
• community II includes residues at the \(i\)th position of \(\mathbf{v}_{k=2}^i<-\text{max}(\mathbf{v}_{k=4}^i, \epsilon)\),
• community III includes residues at the \(i\)th position of \(\mathbf{v}_{k=4}^i>\text{max}(\mathbf{v}_{k=2}^i, \epsilon)\).

The computed RCs are mapped to the tertiary structure (PDB ID: 1AAP).

A conformational change of the G-loop make an extended structure to plug into the head region of the scMdm12Δ and cover the solvent-exposed concave surface of scMdm12Δ². The SAEC method reflects that residue community (in red) is relevant to the conformational change, the two structures of Mmm1 as single domain and in the complex are aligned to each other for comparison. The statistical qualities of the residue communities (in green) do not capture the important information from the G-loop when Mmm1 adopts a shape as a monomer, while the Mmm1 changes its shape via the G-loop (residue community in red) in response to the formation of a complex between the Mmm1 and Mdm12 proteins. Read More >>