Fibroblast büyüme faktörü reseptörü (FGFR3) IIIB için hesaplamalı yöntemlerle pentapeptid inhibitör tasarımı

Fibroblast growth factor receptor (FGFR) is a cell membrane protein, a member of tyrosine kinase family, which has extracellular domains activated by ligand binding, followed by receptor dimerization. FGFR3 has two isoforms, IIIb and IIIc. The IIIb isoforom of FGFR3 is a highly expressed epithelial cell protein, whose R248C mutation causes different kinds of dermatological diseases like seborrheic keratoses (SK), acanthosis nigricans (AN) and epidermal nevi (EN). This mutation leads to ligand independent receptor dimerization, which increases intracellular signaling, resulting in skin diseases. In order to prevent R248C mutation-caused cellular signaling, a pentapeptide ligand is designed that recognizes the mutation and binds to the receptor dimerization site. For this purpose molecular docking and molecular dynamics simulations are conducted. Binding free energy is calculated with Steered Molecular Dynamics (SMD) and Molecular mechanics ? Generalized Born Surface Area (MM-GBSA) methods. The found pentapeptide sequence appears to be a possible drug candidate for FGFR3 IIIb R248C mutation related skin diseases.