In Silico Engineering of Synthetic Binding Proteins from Random Amino Acid Sequences.

ABSTRACT: Synthetic proteins with high affinity and selectivity for a protein target can be used as research tools, biomarkers, and pharmacological agents, but few methods exist to design such proteins de novo. To this end, the In-Silico Protein Synthesizer (InSiPS) was developed to design synthetic binding proteins (SBPs) that bind pre-determined targets while minimizing off-target interactions. InSiPS is a genetic algorithm that refines a pool of random sequences over hundreds of generations of mutation and selection to produce SBPs with pre-specified binding characteristics. As a proof of concept, we design SBPs against three yeast proteins and demonstrate binding and functional inhibition of two of three targets in vivo. Peptide SPOT arrays confirm binding sites, and a permutation array demonstr

SUBMITTER: Burnside D 

PROVIDER: S-EPMC6348295 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature