RoSETTA Obstacles Enhancements Problem 1: generate lots of unrealistic decoys Filter based on contact order, quality of B-sheets, poor packing Problem 2: large search space Bias fragment picking by predicted secondary structure, faster computational algorithms Problem 3: low confidence in the result Fold many homologs of the target cluster the answers, report the cluster with highest occupancyROSETTA Obstacles & Enhancements • Problem 1: generate lots of unrealistic decoys – Filter based on contact order, quality of β-sheets, poor packing • Problem 2: large search space – Bias fragment picking by predicted secondary structure, faster computational algorithms • Problem 3: low confidence in the result – Fold many homologs of the target, cluster the answers, report the cluster with highest occupancy