Computer Simulations of Proteins Help Unravel Why Chemotherapy Resistance Occurs

https://news.stonybrook.edu/university/computer-simulations-of-proteins-help-unravel-why-chemotherapy-resistance-occurs-2/

by rbanffy • 4 years ago

72 8 4 years ago

news.stonybrook.edu

pfisherman2• 4 years ago

Ugh. Source article is behind a paywall!

gumby• 4 years ago

Unfortunately it’s not in sci-hub yet but I imagine it will be soon. You can also look at the authors’ own web sites — often they post their papers there

armeehn• 4 years ago

If you’re OK with the pre-print, here’s the link: https://www.biorxiv.org/content/10.1101/2021.07.02.450932v2

pfisherman2• 4 years ago

Awesome! Thanks!

bawolff• 4 years ago

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.

mbreese• 4 years ago

Without knowing the mechanism of resistance, you wouldn’t risk giving the patient more of a drug. Many resistance mechanisms remove or block the binding pocket drugs bind to. In those cases, adding more frequent dosing wouldn’t be helpful.

You might have tried something like this first in a mouse model too. But using a simulation to discover the resistance mechanism can be a much faster way to get your answer (and justify the expense of a mouse study). This study is quite exciting to see.

dnhz• 4 years ago

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.

gusennan• 4 years ago

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.

Computer Simulations of Proteins Help Unravel Why Chemotherapy Resistance Occurs

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