title: Rhodomyrtone Target Exploration: Computer Aided Search on Staphylococcus aureus Key Proteins as a Potential Therapeutic Target.
abstract: BACKGROUND
  Methicillin-resistant Staphylococcus aureus (MRSA) has been a global public health problem because MRSA infection often leads to poor clinical outcomes. Currently, the search for an effective candidate has been ongoing. Rhodomyrtone, a natural compound, has been exhibited strong anti-MRSA activity comparable to that of vancomycin, a drug of choice for MRSA treatment. An important procedure to develop the compound in clinical use is elucidation of its molecular mechanism. However, previous attempts were performed to clarify the mechanism but ambiguity still exists. With this aspect, computer aided techniques to identify drug targets is able to enhance a success rate in drug discovery.
  
  
  METHODS
  Fifty MRSA proteins, playing roles in vital processes, was screened rhodomyrtone molecular targets. The molecular docking study was operated using AutoDock4. To confirm two possible targets, checkerboard assay and cell visualization were further carried out.
  
  
  RESULTS
  Rhodomyrtone exhibited an interesting efficacy towards one-fifth of the given proteins. Moreover, metaldependent phosphate binding proteins were excluded from possible targets because of electrostatic forces. Amongst chosen proteins, rhodomyrtone, both enantiomers, displayed significant potency to dihydrofolate reductase (DHFR) and filamenting temperature-sensitive Z (FtsZ) proteins, compared to their natural substrates/inhibitors. However, protein cofactors such as nicotinamide adenine dinucleotide phosphate or guanosine diphosphate decreased rhodomyrtone binding affinity. This information suggested a cofactor free DHFR and a ligand-unbound FtsZ are likely to prove to be rhodomyrtone targets for MRSA inhibition. In addition, checkerboard assay and cell visualization gave a hint on target confirmation.
  
  
  CONCLUSIONS
  We have proposed potential rhodomyrtone targets, and DHFR and FtsZ caught our interest. Further studies will need to focus on profound molecular information concerning the rhodomyrtone response to these proteins, both in experimental and computational views.
authors.forename: Dennapa
authors.initials: D
authors.lastname: Saeloh
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla, 90110, Thailand. tvaromya@medicine.psu.ac.th.
authors.forename: Varomyalin
authors.initials: V
authors.lastname: Tipmanee
authors.forename: Supayang P
authors.initials: SP
authors.lastname: Voravuthikunchai
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D044004:Xanthones / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D044004:Xanthones; C541823:rhodomyrtone