Molecular dynamics simulations: A mechanistic probe for understanding antibacterial activity
Journal Title: International Journal of Pharmaceutical Chemistry and Analysis - Year 2017, Vol 4, Issue 3
Abstract
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.
Authors and Affiliations
Arati Prabhu
Keywords
Related Articles
- EP ID EP310589
- DOI 10.18231/2394-2797.2017.0016
- Views 81
- Downloads 0
Successful management of a rare case of Miller Fisher variant of Guillain – Barre Syndrome in rural tertiary care
Guillain-Barre syndrome (GBS) is also known as acute idiopathic polyneuritis. It is a neuromuscular paralysis that occurs in all the age groups and has several variants. These include demyelinating polyneuropathy, acute...
Current perspective of histone deacetylase inhibitors: A review
Epigenetic therapeutics are the new generation of chemotherapeutics for treatment of cancer and histone deacetylase inhibitors have been actively discovered in this category They target the biological processes including...
Method Development and Validation of RP HPLC Method for Assay and related Substances of Luliconazole in Topical Dosage form
A simple, specific, accurate, precise , rapid, robust and selective stability indicating reverse phase high performance liquid chromatography (RP-HPLC) method has been developed for assay and related substances and valid...
Method development and validation of aliskiren in tablet formulation by UV spectrophotometric methods
Optical methods through ultravioletspectrophotometer were developed and justification was done to validate the method for quantitative determination of aliskiren in its tablet formulation Wavelengths for different method...
Formulation and evaluation of sustained release mucoadhesive microspheres of lornoxicam by using novel isolated polymer of fruit artocarpus heterophyllus
Objective To investigate the potential of novel polymer isolated from fruit Artocarpus heterophyllus for mucoadhesion and sustained release action Microspheres containing Lornoxicam formulated using isolated polymer offe...