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3D structure generation, virtual screening and docking of human Ras-associated binding (Rab3A) protein involved in

Sharad S Lodhi1, Rohit Farmer, Atul Kumar Singh

  • 1School of Studies in Biochemistry, Jiwaji University, Gwalior, 474011, India.

Molecular Biology Reports
|March 22, 2014
PubMed

Insights

Researchers modeled the Rab3A protein structure and screened compounds to find potential inhibitors. A top molecule, ZINC13152284, showed promising binding affinity for Rab3A, suggesting it could be a starting point for developing new drugs.

Area of Science:

  • Computational biology and structural bioinformatics
  • Neuroscience and cancer research

Background:

  • Rab3A protein is predominantly expressed in brain and synaptic vesicles.
  • It plays a role in neurotransmitter release, and its upregulation is linked to certain cancers.
  • The precise function of Rab3A remains under investigation.

Purpose of the Study:

  • To model the 3D structure of Rab3A protein.
  • To identify potential high-affinity inhibitors of Rab3A using molecular docking.
  • To analyze protein-ligand interactions for drug development.

Main Methods:

  • Protein structure modeling using MODELLER 9v8.
  • Molecular docking of GTP and small molecules (NCI diversity set II) using GOLD and GLIDE.
  • Analysis of binding affinity and interactions using X-Score and Ligplot.

Main Results:

  • The Rab3A-GTP complex showed a GOLD fitness value of 77.73, with identified hydrogen bonding and hydrophobic interactions.
  • Screening identified five compounds with potential inhibitory activity against Rab3A.
  • The top-ranked compound, ZINC13152284, exhibited strong binding affinity (Glide score: -6.65 kcal/mol, X-Score: -3.02 kcal/mol) with favorable interactions.

Conclusions:

  • Computational modeling and docking successfully identified potential inhibitors for Rab3A.
  • ZINC13152284 represents a promising lead compound for developing novel Rab3A inhibitors.
  • Further studies are warranted to explore the therapeutic potential of these identified compounds.

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