Background: Lipid II, a peptidoglycan, is a precursor in bacterial cell synthesis. It has both
hydrophilic and lipophilic properties. The molecule translocates a bacterial membrane to deliver and
incorporate “building blocks” from disaccharide-pentapeptide into the peptidoglican wall. Lipid II is a
valid antibiotic target. A receptor binding pocket may be occupied by a ligand in various plausible conformations,
among which only few ones are energetically related to a biological activity in the physiological
efficiency domain. This paper reports the mapping of the conformational space of Lipid II in its
interaction with Teixobactin and other Lipid II ligands.
Methods: In order to study computationally the complex between Lipid II and ligands, a docking study
was first carried on. Docking site was retrieved form literature. After docking, 5 ligand conformations
and further 5 complexes (denoted 00 to 04) for each molecule were taken into account. For each structure,
conformational studies were performed. Statistical analysis, conformational analysis and molecular
dynamics based clustering were used to predict the potency of these compounds. A score for potency
prediction was developed.
Results: Appling lipid II classification according to Lipid II conformational energy, a conformation of
Teixobactin proved to be energetically favorable, followed by Oritravicin, Dalbavycin, Telvanicin,
Teicoplamin and Vancomycin, respectively. Scoring of molecules according to cluster band and PCA
produced the same result. Molecules classified according to standard deviations showed Dalbavycin as
the most favorable conformation, followed by Teicoplamin, Telvanicin, Teixobactin, Oritravicin and
Vancomycin, respectively. Total score showing best energetic efficiency of complex formation shows
Teixobactin to have the best conformation (a score of 15 points) followed by Dalbavycin (14 points),
Oritravicin (12v points), Telvanicin (10 points), Teicoplamin (9 points), Vancomycin (3 points).
Conclusion: Statistical analysis of conformations can be used to predict the efficiency of ligand - target
interaction and consecutively to find insight regarding ligand potency and postulate about favorable conformation
of ligand and binding site. In this study it was shown that Teixobactin is more efficient in binding
with Lipid II compared to Vancomycin, results confirmed by experimental data reported in literature.