title: Comparative reverse screening approach to identify potential anti-neoplastic targets of saffron functional components and binding mode.
abstract: BACKGROUND
  In the last two decades, pioneering research on anti-tumour activity of saffron has shed light on the role of crocetin, picrocrocin and safranal, as broad spectrum anti-neoplastic agents. However, the exact mechanisms have yet to be elucidated. Identification and characterization of the targets of bioactive constituents will play an imperative role in demystifying the complex anti-neoplastic machinery.
  
  
  METHODS
  In the quest of potential target identification, a dual virtual screening approach utilizing two inverse screening systems, one predicated on idTarget and the other on PharmMapper was here employed. A set of target proteins associated with multiple forms of cancer and ranked by Fit Score and Binding energy were obtained from the two independent inverse screening platforms. The validity of the results was checked by meticulously analyzing the post-docking binding pose of the picrocrocin with Hsp90 alpha in AutoDock.
  
  
  RESULTS
  The docking pose reveals that electrostatic and hydrogen bonds play the key role in inter-molecular interactions in ligand binding. Picrocrocin binds to the Hsp90 alpha with a definite orientation appropriate for nucleophilic attacks by several electrical residues inside the Hsp90-alpha ATPase catalytic site.
  
  
  CONCLUSIONS
  This study reveals functional information about the anti-tumor mechanism of saffron bioactive constituents. Also, a tractable set of anti-neoplastic targets for saffron has been generated in this study which can be further authenticated by in vivo and in vitro experiments.
authors: Department of Biotechnology, PES Institute of Technology, Bangalore, India. biplabbhattacharjee2010@gmail.com
authors: Biplab
authors: B
authors: Bhattacharjee
authors: Sandhya
authors: S
authors: Vijayasarathy
authors: Prashantha
authors: P
authors: Karunakar
authors: Jhinuk
authors: J
authors: Chatterjee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites; D002338:Carotenoids / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D027622:Crocus / Q000737:chemistry / Q000378:metabolism*; D053138:Cyclohexenes / Q000737:chemistry / Q000494:pharmacology; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology; D014584:User-Computer Interface; D014801:Vitamin A / Q000031:analogs & derivatives
chemical_list: D000970:Antineoplastic Agents; D053138:Cyclohexenes; D005960:Glucosides; D018841:HSP90 Heat-Shock Proteins; C533585:HSP90AA2P protein, human; D013729:Terpenes; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; C087963:safranal; C087962:picrocrocin