FuncLib is an automated method to design and rank epistatic multipoint mutants at enzyme active sites using phylogenetic analysis and Rosetta atomistic design calculations.
FuncLib starts by computing single-point active-site mutations that are likely to be tolerated, and then exhaustively models each combination of mutants, ranks them by energy, and selects the top designs as recommendations for experimental testing.
After calculations, the user receives an email with the top scoring 50 designs.
Since the method is exhaustive, as more mutations and positions are tested, the task becomes more computationally demanding. At this point, we only allow a maximum of half a million designs to be scored and ranked and the server will return an error if the number of designs that are implied by the tolerated sequence space exceeds this number.
We are developing methods for dealing with larger sequence spaces, and if that is necessary for your application, please contact us.
- Original FuncLib paper Automated Design of Efficient and Functionally Diverse Enzyme Repertoires Khersonsky et al. Mol. Cell (2018)
- Design of variable light heavy interface Optimizing antibody affinity and stability by the automated design of the variable light-heavy chain interfaces. Warszawski et. al., Plos. Comp. Biol.
- Protein-protein interfaces Ultrahigh specificity in a network of computationally designed protein-interaction pairs. Netzer et al., Nature Commun (2018)
- htFuncLib Designed active-site library reveals thousands of functional GFP variants. Weinstein et al. bioRxiv (2022)