Oncogenic PI3Kα variants are key drivers of tumorigenesis; however, the conformational landscape of these mutants is not well characterized. Here, the authors use atomistic molecular dynamics simulations to show that double mutations in PI3Kα induce significant conformational shifts, revealing cryptic druggable pockets within PI3Kα and providing a rationale for using allosteric drug combinations in targeted therapy.
- Hyunbum Jang
- Bengi Ruken Yavuz
- Ruth Nussinov
