title: Combination Assays and Molecular Docking can Identify Binding sites of Anti-Microtubule Drugs on Plasmodium falciparum Tubulin.
abstract: BACKGROUND
  Lead compounds that target tubulin are being developed as agents against the human malaria parasite, Plasmodium falciparum. It is important to define the binding sites of these molecules on the tubulin dimer: Taxol, Vinca domains or novel binding pockets; however, extraction of native parasite tubulin is difficult.
  
  
  OBJECTIVE
  This report aims to develop assays that allow the rapid assessment of binding sites of compounds on the tubulin dimer.
  
  
  METHODS
  We have developed a simple growth assay, using a combination of two anti-microtubule drugs that have overlapping binding sites, to study whether the two drugs act in synergistic, antagonistic or neutral manner. Additionally, Molecular docking was used to predict the binding sites of the drugs.
  
  
  RESULTS
  The combination assay shows antagonistic interactions between drugs having overlapping binding sites. In contrast, drugs that do not bind to overlapping sites show no interactions or synergism in this combination assay. Molecular docking predictions show that indeed, drugs with antagonistic interactions in the growth assay do bind to overlapping sites.
  
  
  CONCLUSIONS
  These two assays can be a simple preliminary screen for the binding sites of novel anti-tubulin compounds being developed for malaria therapeutics.
authors.forename: Rimi
authors.initials: R
authors.lastname: Chakrabarti
authors.affiliation: Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, India. patankar@iitb.ac.in.
authors.forename: Swati
authors.initials: S
authors.lastname: Patankar
mesh_terms: D001665:Binding Sites; D004347:Drug Interactions; D006801:Humans; D008870:Microtubules / Q000737:chemistry; D062105:Molecular Docking Simulation; D017239:Paclitaxel / Q000378:metabolism / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism; D050257:Tubulin Modulators / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D014404:Tubulin; D050257:Tubulin Modulators; D017239:Paclitaxel