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.

摘要

成纤维细胞生长因子 10 作为旁分泌间充质分子发挥作用，以启动有关细胞发育和健康的信号通路。然而，低热稳定性限制了它在人体中的功能和基于 FGF10 的配方的保质期。目前的研究旨在采用合理的设计和生物信息学方法来识别一些可能提高 FGF10 热稳定性的点突变。生物信息学分析导致​​ N105D、C106F、K144R、K153M 和 I156R 作为潜在的稳定性赋予突变。对鉴定的突变体进行 MD 模拟，表明所有突变在结构上和能量上都是有利的。最后，预测了所鉴定的突变对 FGF10 受体结合的影响，结果表明，K144R 和 K153M 突变可能会增加相对于野生型的结合亲和力。当前研究的结果提出了可能改进的 FGF10 类似物，用于进一步的实验研究。