Human Glucosylceramide Synthase at Work as Provided by "In Silico" Molecular Docking, Molecular Dynamics, and Metadynamics.

ABSTRACT: Glucosylceramide synthase (GCS) is an enzyme that catalyzes the first reaction of ceramide glycosylation in sphingolipid metabolism. It represents a primary target in the pharmacological treatment of some lysosomal storage diseases (LSDs), such as Gaucher and Niemann-Pick syndromes. In this study, starting from the model reported in the AlphaFold Protein Structure Database, the location and conformations of GCS substrates and cofactors have been provided by a step-by-step in silico procedure, by which the functional manganese ion and the substrates have been inserted in the GCS structure through combined molecular docking and full-atomistic molecular dynamics approaches, including metadynamics. A detailed analysis by structural dynamics of the complete model system, i.e., the enzyme

SUBMITTER: Canini G 

PROVIDER: S-EPMC9996764 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature