GENERATION AND SELECTION OF PROTEIN LIBRARY IN SILICO

摘要

GENERATION AND SELECTIONThe present invention provides a methodology for efficientlygenerating and screening protein libraries for optimized proteins withdesirable biological functions, such as improved binding affinity towardsbiologically and/or therapeutically important target molecules. Theprocess is carried out computationally in a high throughput manner bymining the ever-expanding databases of protein sequences of allorganisms, especially human. In one embodiment, a method forconstructing a library of designed proteins, comprising the steps of:providing an amino acid sequence derived from a lead protein, theamino acid sequence being designated as a lead sequence; comparingthe lead sequence with a plurality of tester protein sequences; andselecting from the plurality of tester protein sequences at least twopeptide segments that have at least 15% sequence identity with the leadsequence, the selected peptide segments forming a hit library; andforming a library of designed proteins by substituting the lead sequencewith the hit library. The library of designed proteins can be expressedin vitro or in vivo to produce a library of recombinant proteins that canbe screened for novel or improved function(s) over the lead protein, suchas an antibody against therapeutically important target.(No suitable figure)