Pro1 was prompted to optimize FGF-1 for improved thermostability while retaining its clinically relevant properties. The prompt included general information about FGF-1 (function, known interactions), mutagenesis data from UniProt, and select excerpts from papers that have previously engineered more stable FGF-1 variants.

The base and creative model instances were sampled 50 times each, with the top 10 variants from each (by rosetta energy score) selected for further validation.

Example excerpts from prompt:

“For the heterodimer of FGF1 and FGF2 contains two mutations within the FGF-1 portion of the dimer, R136E and K126N. These mutations were induced to negate the overwhelming positive charge present in the heparin binding pocket (HBP) of FGF-1 and were found to increase the overall stability of the protein, increase cell proliferation activity, and decrease heparin binding affinity.” (McClanahan, 2022)

“Binds to integrin ITGAV:ITGB3. Its binding to integrin, subsequent ternary complex formation with integrin and FGFR1, and the recruitment of PTPN11 to the complex are essential for FGF1 signaling.” (Mori, 2008)