| 摘要 |
The invention is directed to methods for obtaining statistically significant information about how structural elements of proteins, e.g. position and identity of amino acid residues in binding domains, relate to functional properties of interest, such as binding affinity, specificity, and the like. In some embodiments, such information is collected by reacting under binding conditions a focused library of candidate nucleic acid-encoded binding compounds with a ligand, so that complexes form between the ligand and a portion of the candidate binding compounds (“binders”). Samples of binders and non-binders arc then decoded by high throughput nucleic acid sequencing to give statistically significant data about the binding properties of substantially all of the candidate binding compounds, permitting them to be ranked by their respective affinities or dissociation constants. A reference compound, such as a pre-existing antibody, may be included in the reaction to identify candidates with similar or improved binding characteristics that have additional desirable characteristics, such as higher solubility, reduced immunogenicity, higher stability, or the like. |
