ABSTRACT
The present investigation was carried out with the aim of modeling the 3D structure of FGFR3 protein and predicting the most effective drug using SU5402 and its analogues. FGFR3 protein, responsible for long bone growth, causes Achondroplasia in H. sapiens when it becomes mutated. When mutated, the dimmer of FGFR3 stabilizes without interacting with its ligand results in constitutive activation of downstream pathway and inhibits the bone growth. No known structure of FGFR3 was available. The 3D modeling of FGFR3 was done using Robetta server and from the various model predicted, model 5 was selected as the best model after evaluating the models using PROCHECK. . The total number of residues in selected model was found as: 589 (86.5%) residues in most favored region, 84 (12.3%) in additional allowed region, 8 (1.2%) in generously allowed region and 0 (0.0%) in disallowed region of the Ramachandran plot. Three analogues were constructed by using the existing FGFR3 specific inhibitor SU5402. Receptor-analogue interaction study was performed in FlexX3 docking software. Ligand 3 (IUPAC Name: 3-{2-[Z)-(4-hydroxy-2-oxo-1,2-dihydro-3Hindol- 3-ylidene) methyl]-4-oxo-4,5-dihydro-1H-pyrrol-3-yl} propanoic acid) was showing the best binding energy (-10.458 KJ/Mol) that can be predicted the most effective inhibitor for FGFR3. It should be noted that these predicted data should be validated using suitable assays for further consideration.