Volume : 4
Issue : 3
Online ISSN : 2394-2797
Print ISSN : 2394-2789
Article First Page : 66
Article End Page : 69
Introduction: Molecular dynamics, in which molecules are allowed to interact over time at a given temperature following the laws of classical mechanics has been shown to be highly successful in simulating various biological phenomena down to atomic detail. When applied to complexes of protein targets and potential binders, this technique, provides a detailed description of the stability of the protein-ligand complexes, thereby throwing light on the binding potential of the ligands to probable target proteins.
Materials and Method: In the present study we have explored the mechanism of protein synthesis inhibition by the antibiotic thiostrepton with the combination of manual docking followed by molecular dynamics simulations to two molecular targets – the L11/23S-rRNA interface and the elongation factor Ef-Tu. Cross-docking runs on the two native co-crystallised ligands of the target proteins were done as a further probe.
Results: Docking of thiostrepton at the L11/23S-rRNA interface as well as Ef-Tu indicated stable binding during 10-ns molecular dynamics simulations, whereas LFF571 binds stably only to its native protein EF-Tu which is in accordance to literature reports. Thus, molecular dynamics simulation studies indicate that thiostrepton has binding potential to two targets of protein synthesis translation, the elongation factor (Ef-Tu) and L11 protein and 23S-rRNA interface.
Conclusion: This study corroborates that thiostrepton inhibits Ef-Tu in addition to the L11-ribosomal RNA complex. Binding to multiple targets probably enhances its inhibitory effect on protein translation.
Keywords: Thiazolyl peptide, Macrocyclic, Ef-Tu, Molecular dynamics simulations, Thiostrepton, Ribosome