title: Identification of Novel Antagonists for Rab38 Protein by Homology Modeling and Virtual Screening.
abstract: BACKGROUND
  The Rab family proteins are involved in membrane trafficking, cell growth and differentiation. Rab38 is implicated in the biogenesis of melanosomes that help in the synthesis, storage and transport of melanin pigments. The Rab38 protein is overexpressed at the RNA level in melanoma cancer.
  
  
  OBJECTIVE
  The protein Rab38 is targeted for identification of novel antagonists as cancer drug candidates.
  
  
  METHODS
  The 3D structure of Rab38 was generated using homology modelling method. The 3D model was validated. The active site was identified by using standard computational prediction tools like CASTp, efindsite and SiteMap. The study of protein-protein docking was performed between Rab38 and its natural substrate BLOC-3 using patchDock server tool. Virtual screening protocols were carried out using glide module. Various informatics tools like 1) Schrodinger Suite 2) Modeller 3) Accelrys Discovery Studio 4) PyMOL 5) SPDBV etc. are applied for the identification of novel inhibitors of Rab38.
  
  
  RESULTS
  The residues from SER35 to LEU63 of Rab38 protein are important for binding to ligands. The nineteen docked structures were obtained as an output of virtual screening. The compounds obtained show good glide score, and a common binding pattern at the active site.
  
  
  CONCLUSIONS
  The benzosulfonamide and heterocyclic nitrogen moieties may be considered as pharmacophores for designing new anticancer leads with better docking score and admissible ADME properties. Our study helps in the identification of potential inhibitors against Rab38 and melanoma cancer.
authors: Aboubakr Haredi
authors: AH
authors: Abdelmonsef
authors: Ramasree
authors: R
authors: Dulapalli
authors: Thirupathi
authors: T
authors: Dasari
authors: Lavanya Souda
authors: LS
authors: Padmarao
authors: Thirupathi
authors: T
authors: Mukkera
authors: Department of Chemistry, University College of Science, Osmania University, Hyderabad 500007, Telangana, India.. India.
authors: Uma
authors: U
authors: Vuruputuri
mesh_terms: D000595:Amino Acid Sequence; D062105:Molecular Docking Simulation; D017386:Sequence Homology, Amino Acid; D020691:rab GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: C412058:RAB38 protein, human; D020691:rab GTP-Binding Proteins
keywords: G proteins; Rab38; homology modelling; melanoma; protein-protein docking.; virtual screening