Abstract
Background: FGF7 is a potent cytoprotective and regenerative protein on the injured epithelial tissues, indicating its potential therapeutic effect in conditions such as mucositis, ulcerative colitis, and cutaneous wound formation induced by chemotherapy or radiotherapy. However, FGF7 low stability prevents its usability as a pharmaceutical product, necessitating the design and production of stable FGF7 mutants.
Methods: In the current study, bioinformatics and MD simulations approaches were used for identifying potential stable mutants of FGF7. For this, the model structure of FGF7 was constructed and subjected to MAESTROweb service to identify stability conferring mutations. The identified potential mutants of FGF7 were MD simulated in an explicit denaturant condition and their stabilities were evaluated. The complexes of FGF7 mutants with FGFR2 receptor were also examined to investigate the receptor binding ability of proposed mutants.
Results: Investigation of stability parameters showed that introducing A104S mutations in FGF7 may greatly improve its stability in urea solution. Calculation of binding energies indicated that A104S mutant interacts better then wild type FGF7 with the receptor. The structural stability and binding capability of A104S were comparable to that of A120C mutation, as an experimentally determined stability conferring mutation, which was used in whole process to indicate the validity of employed MD simulation for predicting the effect of mutation on FGF7 stability.
Conclusion: The results of current study showed that A104S mutant of FGF7 has a potential to be evaluated further for the purpose of presenting a therapeutic agent effective in conditions such as mucositis, ulcerative colitis, and cutaneous wound formation induced by chemotherapy or radiotherapy.