Xiao-Shuai Cheng

A Kinetic Origin of Vps34-IN-3 Selectivity for VPS34 over PI3Kα Revealed by Supervised Molecular Dynamics and Potential of Mean Force Analysis.

The rational design of selective kinase inhibitors is hampered by the conserved ATP-binding pockets. Vps34-IN-3, a potent VPS34 inhibitor developed by Genentech, Inc., showed ∼95-fold selectivity over the closely related PI3Kα, yet the atomic-level mechanism underlying this selectivity remains unclear. Here, we combine...