Time saving approach to design altered ligand structure

To find energetically advantageous variants of the structure of the peptide ligand complexing with the proteins of the major histocompatibility complex and the T-cell receptor (SwissProt ID: 2Z31), the binding energy of hexamers, which are fragments of the native ligand structure, was compared. To form a set of investigated hexamers, the Taguchi method was used. In total, 53 variants of the structure of the complex were constructed and investigated using molecular dynamics. Calculations were carried out both for complete complexes and for free structures - receptors and ligands. On the basis of the obtained molecular trajectories, using the generalized Born method, the free energy of the structures was calculated and averaged for each trajectory. Using the Taguchi method to analyze the peptide hexamer sequence, it was possible to determine prototypes of the ligand whose structures have a higher binding energy to the receptor than the fragment of the original SQYRPS ligand. The applied approach significantly reduces the time required for optimization of the peptide ligand structure.