Identification of Novel Antagonists for Rab38 Protein by Homology Modeling and Virtual Screening

• Published in: Combinatorial chemistry & high throughput screening Vol. 19; no. 10; p. 875
• Main Authors: Abdelmonsef, Aboubakr Haredi, Dulapalli, Ramasree, Dasari, Thirupathi, Padmarao, Lavanya Souda, Mukkera, Thirupathi, Vuruputuri, Uma
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2016
• Subjects: Amino Acid Sequence; Molecular Docking Simulation; rab GTP-Binding Proteins - antagonists & inhibitors; rab GTP-Binding Proteins - chemistry; Sequence Homology, Amino Acid; homology modelling; Rab38; melanoma; G proteins; virtual screening; protein-protein docking
• ISSN: 1875-5402
• DOI: 10.2174/1386207319666161026153237

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. The protein Rab38 is targeted for identification of novel antagonists as cancer drug candidates. 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. 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. 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.