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Computer-assisted engineering of hyperstable fibroblast growth factor 2

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DVOŘÁK Pavel BEDNÁŘ David VAŇÁČEK Pavel BÁLEK Lukáš EISELLEOVÁ Lívia ŠTĚPÁNKOVÁ Veronika ŠEBESTOVÁ Eva BOSÁKOVÁ Michaela KONEČNÁ Žaneta MAZURENKO Stanislav KUNKA Antonín VÁŇOVÁ Tereza ZOUFALOVÁ Karolína CHALOUPKOVÁ Radka BREZOVSKÝ Jan KREJČÍ Pavel PROKOP Zbyněk DVOŘÁK Petr DAMBORSKÝ Jiří

Druh Článek v odborném periodiku
Časopis / Zdroj Biotechnology and Bioengineering
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www One Library Wiley
Doi http://dx.doi.org/10.1002/bit.26531
Klíčová slova computational design; embryonic stem cells; fibroblast growth factor; focused directed evolution; protein engineering; protein stability
Popis Fibroblast growth factors (FGFs) serve numerous regulatory functions in complex organisms, and their corresponding therapeutic potential is of growing interest to academics and industrial researchers alike. However, applications of these proteins are limited due to their low stability. Here we tackle this problem using a generalizable computer-assisted protein engineering strategy to create a unique modified FGF2 with nine mutations displaying unprecedented stability and uncompromised biological function. The data from the characterization of stabilized FGF2 showed a remarkable prediction potential of in silico methods and provided insight into the unfolding mechanism of the protein. The molecule holds a considerable promise for stem cell research and medical or pharmaceutical applications.
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