cmet lig_CHEMBL3402761_1_21: Should this ligand be charged or neutral?

OpenFreeEnergy / protein-ligand-benchmark

Protein-Ligand Benchmark Dataset for Free Energy Calculations

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cmet lig_CHEMBL3402761_1_21: Should this ligand be charged or neutral? #6

Closed hannahbaumann closed 10 months ago

hannahbaumann commented 1 year ago

Ligand lig_CHEMBL3402761_1_21 has a tertiary amine which is not positively charged (but used to be protonated in the Hahn et al. PLB). Is the pKa maybe near the assay pH? Would one have to account for both protonation states in the benchmark calculations or would it make sense to just stick with one protonation state and use that for all benchmarking exercises?

hannahbaumann commented 1 year ago

The morpholine is pointing towards the solvent and is not buried in the binding pocket.

hannahbaumann commented 1 year ago

For this ligands, the Hahn et al PLB has the charged amine here, while the Schrodinger prepared structure has the neutral amine.

hannahbaumann commented 12 months ago

From this pka prediction (done with Simulations Plus ADMETpredictor V.11 in the context of the OPEN-FF consortium for method development) it looks like the ligand is neutral at pH7