PT - JOURNAL ARTICLE AU - Michael W. Dorrity AU - Christine Queitsch AU - Stanley Fields TI - High-throughput identification of dominant negative polypeptides in yeast AID - 10.1101/418608 DP - 2018 Jan 01 TA - bioRxiv PG - 418608 4099 - http://biorxiv.org/content/early/2018/09/15/418608.short 4100 - http://biorxiv.org/content/early/2018/09/15/418608.full AB - Dominant negative polypeptides can act as inhibitors by binding to the wild type protein or by titrating an essential ligand. Here, we use high-throughput sequencing of DNA libraries composed of fragments of yeast genes to identify dominant negative polypeptides based on their depletion during cell growth. The method uncovers numerous inhibitory polypeptides for a protein and thus is capable of defining interacting domains with exquisite resolution, even pinpointing individual residues that contact ligands.