We noticed while doing post-analysis of our results that the catalytic aspartyl dyad (Asp32, Asp228) of BACE-1 in the prepared protein structure for 4EWO had both aspartates in the protonated form (i.e., Asp32 H , Asp228 H ). This is a possible source of error, because in the apo state, Asp32 is protonated and Asp228 is de-protonated in the active pH range (3.5-5.5) of BACE-1 . Although the protonation state of the aspartyl dyad changes in the presence of inhibitors , it is a safer choice to model the aspartyl dyad as Asp32 protonated, and Asp228 de-protonated (Asp32 H , Asp228 -).