Skip to main content
. Author manuscript; available in PMC: 2022 Sep 1.
Published in final edited form as: Wiley Interdiscip Rev Comput Mol Sci. 2021 Mar 1;11(5):e1521. doi: 10.1002/wcms.1521

Figure 8.

Figure 8.

GaMD simulations revealed the activation and its ε cleavage mechanisms of γ-secretase in the wildtype and mutant APP substrates. Summary of the (A) inactive cryo-EM, (B) active (wildtype), and (C) shifted active (M51F) conformational states of the APP-bound γ-secretase. Distinct AICD products were generated from the wildtype and M51F mutant APP. GaMD free energy profiles of (D) wildtype and (E) M51F APP-bound γ-secretase regarding the Asp257:Cγ–Asp385:Cγ and Asp257:protonated O–Leu49:O distances. Adapted with permission from Bhattarai et al. (2020). Copyright 2020 American Chemical Society. https://pubs.acs.org/doi/abs/10.1021/acscentsci.0c00296. Further permissions related to the material excerpted should be directed to the American Chemical Society.