Fibroblast growth factor receptor (FGFR) is a cell membrane protein and a member of the tyrosine kinase family. It has extracellular domains that can be activated by ligand binding, followed by receptor dimerization. FGFR3 has 2 isoforms, 3b and 3c. | Turkish Journal of Biology Research Article Turk J Biol (2013) 37: 675-682 © TÜBİTAK doi: Computational design of a pentapeptide inhibitor for fibroblast growth factor receptor 3b (FGFR3b) Mehmet Ali ÖZTÜRK*,** Computational Science and Engineering Graduate Program, Koç University, Sarıyer, İstanbul, Turkey Received: Accepted: Published Online: Printed: Abstract: Fibroblast growth factor receptor (FGFR) is a cell membrane protein and a member of the tyrosine kinase family. It has extracellular domains that can be activated by ligand binding, followed by receptor dimerization. FGFR3 has 2 isoforms, 3b and 3c. The R248C mutation in FGFR3b leads to ligand independent receptor dimerization and results in different kinds of dermatological diseases such as seborrheic keratoses, acanthosis nigricans, and epidermal nevi. In order to prevent the increased cellular signaling caused by the R248C mutation, a pentapeptide ligand was designed that recognizes the mutation and binds to the receptor dimerization site. Molecular docking and steered molecular dynamics simulations were conducted, and binding free energy was calculated. The identified pentapeptide sequence appears to be a possible drug candidate for FGFR3b R248C mutation-related skin diseases. Key words: FGFR3b, peptide drug, binding free energy, steered molecular dynamics 1. Introduction Receptor tyrosine kinases form a large family of membrane proteins that have an extracellular domain activated by ligand-binding–induced receptor dimerization. Depending on the cell type and its environment, the receptor dimerization triggers different responses such as cell migration, proliferation, differentiation, and apoptosis. The family of fibroblast growth factor receptors (FGFRs) contains 4 proteins that are generally involved in normal angiogenesis and embryonic development. Structurally, the FGFRs have an .
