The Structure and Dynamics of the Enzyme–Substrate Complex of N-Acetylaspartylglutamate Synthase According to the Computer Simulation Data

Abstract— N-Acetylaspartylglutamate (NAAG) is the most common dipeptide in brain cells, which is synthesized using the enzyme N-acetylaspartylglutamate synthase. In this study, we utilize bioinformatics methods to predict the protein structure based on the primary sequence of the coding gene, classical molecular dynamics to obtain a stable protein complex with N-acetylaspartate and glutamate ligands within the trajectory, and machine learning methods to analyze, describe, and select potential reactive and nonreactive conformations of the model system describing the enzyme–substrate complex. Molecular dynamics trajectories are obtained for a set of selected conformations within the framework of the method of combined quantum and classical molecular mechanics, and the active site of the protein–ligand complex and potential reaction mechanism are characterized.