PLAC Dataset Tests Whether MM/GBSA Can Predict How PTMs Shift Ligand Binding
- The authors curated PLAC, an experimentally validated set of ligand activity changes caused by post-translational modifications; affecting PTMs tend to sit closer to the ligand than neutral ones.
- They benchmarked end-point MM/GBSA protocols across MD lengths and internal dielectric constants.
- Longer MD with a higher dielectric gave the best correlation with experiment, while a lower dielectric classified enhance/weaken/neutral better.
💡 Points
Nobody builds SAR around a PTM state, yet it can quietly explain why a potent binder fails in cells. A curated benchmark is worth more to me than yet another scoring tweak, because we finally have something to test against. The dielectric trade-off between ranking and classification is a useful warning: pick the protocol for the question you are actually asking.