Computer-assisted engineering of hyperstable fibroblast growth factor 2

Biotechnol Bioeng. 2018 Apr;115(4):850-862. doi: 10.1002/bit.26531. Epub 2018 Jan 24.


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.

Keywords: computational design; embryonic stem cells; fibroblast growth factor; focused directed evolution; protein engineering; protein stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Computer Simulation
  • Computer-Aided Design*
  • Directed Molecular Evolution
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Fibroblast Growth Factor 2 / chemistry
  • Fibroblast Growth Factor 2 / genetics*
  • Fibroblast Growth Factor 2 / metabolism*
  • Humans
  • Point Mutation
  • Protein Engineering*
  • Protein Folding
  • Protein Stability*


  • Fibroblast Growth Factor 2