Computer Simulations of Proteins Help Unravel Why Chemotherapy Resistance Occurs

Terrible pop sci title that makes the work sound a bigger deal than it is. I thought that evolution of cancer under drug treatment would be described. But a more accurate title would be, Computer simulations of proteins show molecular mechanism of particular resistance mutations to imatinib that were previously characterized to increase ligand dissociation kinetics.

That is, certain mutations in the protein that the drug imatinib inhibits enable cancer cells to be more resistant to the drug. A previous experimental study by the researchers found that these mutations increase the rate of drug unbinding from the protein. The study here describes computer simulations of the protein and explains why the mutations lead to increased dissociation kinetics. An advanced algorithm was used to sample ligand unbinding events in simulation.

> Additionally, if rapid drug release could cause drug resistance, and clinicians can show this is happening, they may be able to re-activate the drug effectiveness by asking the patient to take the drug more frequently.

One would have thought they would have tried this even without a fancy computer simulation.

I am in a lab that does similar research on resistance to cancer therapeutics but using different computational modeling methods. This is really interesting stuff, as kinetics as a method of resistance has been something that we know is important from a biological perspective but hasn't yet been incorporated much in resistance modeling.

Ugh. Source article is behind a paywall!