Mechanism of glucocerebrosidase activation and dysfunction in Gaucher disease unraveled by molecular dynamics and deep learning

Abstract

Significance Gaucher disease is a rare genetic disorder that has crippling health consequences. Mutations in the GBA1 gene are known to disrupt the enzyme glucocerebrosidase-1, but it is not known, at atom-level detail, as to how enzyme function is lost. This study uses multiscale simulations and deep learning to define precisely the mechanism underlying the disruption of glucocerebrosidase-1 and, in particular, its interaction with the facilitator protein, saposin C.