Application of bioinformatics and molecular dynamics simulation approaches for identification of fibroblast growth factor 10 analogues with potentially improved thermostability.

Growth Factors
Ali Akbar AlizadehSiavoush Dastmalchi

Abstract

Fibroblast growth factor 10 functions as a paracrine mesenchymal molecule to initiate signalling pathways regarding to cellular development and health. However, the low thermal stability restricts it's functionality in the human body and the shelf-life of FGF10-based formulations. The current study aimed to employ rational design and bioinformatics approaches to identify some point mutations which may improve the thermal stability of FGF10. Bioinformatics analyses resulted in N105D, C106F, K144R, K153M and I156R as the potential stability conferring mutations. The identified mutants were subjected to MD simulation indicating that all mutations are both structurally and energetically favoured. Finally, the effects of the identified mutations on receptor binding of FGF10 were predicted and the results showed that K144R and K153M mutations may increase the binding affinity relative to the wild type. The findings of the current study propose potentially improved FGF10 analogues for further experimental investigations.

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