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Volume 12   Issue 2   Year 2017
Time Saving Approach to Design Altered Ligand Structure

Danilkovich A.V., Tikhonov D.A., Turobov V.I., Udovichenko I.P.

Branch of the M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Russia
Pushchino State Institute of Natural Sciences, Pushchino, Russia
Institute of Mathematical Problems of Biology – Branch of Keldysh Institute of Applied Mathematics of Russian Academy of Sciences, Pushchino, Russia
Institute of Theoretical and Experimental Biophysics RAS, 
Pushchino, Russia

Abstract. 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.
Key words: Taguchi method, structure optimization, Gibbs energy, spatial model, molecular dynamics.
Table of Contents Original Article
Math. Biol. Bioinf.
doi: 10.17537/2017.12.446
published in Russian

Abstract (rus.)
Abstract (eng.)
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