Molecular dynamics simulations provide evidence that 35INS could cause imatinib resistance similar to the T315I case, mainly due to imatinib binding mode changes. (Left) The overlap view (upper: overall structure; lower: imatinib and C-Helix) of the ABL-imatinib complex from the wild-type ABL crystal structure (yellow) and the homology modeling structure of the 35INS mutant (red). (Right) The same view but from the homology modeling structure (red) and the snapshot of molecular dynamics simulation at 20 ns (light blue) of the 35INS mutant. The drug imatinib is shown in green in all panels. Note that the backbone atoms of C-Helix almost have the same positions in wt and homology modeling structures while their positions change significantly in the simulation structure. For details, see Lee et al., in this issue.