Amino Acids in Nine Ligand-Prefer Ramachandran Regions

Abstract EN

Several secondary structures, such as π-helix and left-handed helix, have been frequently identified at protein ligand-binding sites.

A secondary structure is considered to be constrained to a specific region of dihedral angles.

However, a comprehensive analysis of the correlation between main chain dihedral angles and ligand-binding sites has not been performed.

We undertook an extensive analysis of the relationship between dihedral angles in proteins and their distance to ligand-binding sites, frequency of occurrence, molecular potential energy, amino acid composition, van der Waals contacts, and hydrogen bonds with ligands.

The results showed that the values of dihedral angles have a strong preference for ligand-binding sites at certain regions in the Ramachandran plot.

We discovered that amino acids preceding the ligand-prefer ϕ/ψ box residues are exposed more to solvents, whereas amino acids following ligand-prefer ϕ/ψ box residues form more hydrogen bonds and van der Waals contacts with ligands.

Our method exhibited a similar performance compared with the program Ligsite-csc for both ligand-bound structures and ligand-free structures when just one ligand-binding site was predicted.

These results should be useful for the prediction of protein ligand-binding sites and for analysing the relationship between structure and function.