Protein design algorithms predict viable resistance to an experimental antifolate

• DOI: 10.1073/pnas.1411548112
• Publication Date: 2015-01-01T03:20:09Z
• Authors: Stephanie M. Reeve; Pablo Gainza; Kathleen M. Frey; Ivelin Georgiev; Bruce R. Donald; Amy C. Anderson
• Keywords: Antifolate; Dihydrofolate reductase

Significance Computationally predicting drug resistance mutations early in the discovery phase would be an important breakthrough development. The most meaningful predictions of target will show reduced affinity for while maintaining viability complex context a cell. Here, protein design algorithm K* Osprey was used to predict single-nucleotide polymorphism dihydrofolate reductase that confers experimental antifolate preclinical phase. Excitingly, mutation also selected bacteria under pressure, confirming prediction viable molecular response external stress.