Computational protocol: Regulating the effects of GPR21, a novel target for type 2 diabetes

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Protocol publication

[…] An in-house GPR21 structural model was constructed using the Modeller software embedded in Biovia Discovery Studio. A sequence alignment was constructed between the amino acid sequence of the GPCR templates (2RH1, 4GBR), with the hGPR21 (Swissprot accession code Q99679), and manually inspected to confirm the correct alignment of conserved residues. Using the alignment, 1,000 different models were generated with a subsequent refinement protocol applied to the loop regions. Disulfide bonds were formed between Cys102 and Cys181. The final model was selected using the Modeller objective score and a selection of protein assessment tools (http://services.mbi.ucla.edu/SAVES/).Utilising this developed protein model, virtual screening processes were implemented to examine large compound databases (e.g. Specs, www.specs.net) in silico through molecular docking studies (OpenEye, Fred). The molecules were standardised, and tautomers and stereoisomers were enumerated using Biovia Pipeline Pilot. Conformers were generated using Omega from Openeye prior to docking using default parameters with Fred and scoring with the chemgauss3 scoring function. From the ranked list, 11 compounds were ordered for experimental validation. […]

Pipeline specifications

Software tools MODELLER, BIOVIA Discovery Studio
Application Protein structure analysis
Organisms Mus musculus
Diseases Diabetes Mellitus, Metabolic Diseases, Machado-Joseph Disease