MM-PBSA binding affinity calculations based on 50ns MD simulations for dabrafenib (DB) and its metabolites carboxy-dabrafenib (CDB), desmethyl-dabrafenib (DDB), and hydroxy-dabrafenib (HDB) with BRAF-V600E (see Figure ) and with BRAF-WT with a structured, helical activation loop (see Figure ) are dependant on the solute dielectric constant ( ). Especially the charged CDB shows an inverted behaviour compared to the other three molecules.