Computational evaluation of EPA-PC binding to GCase in neuronopathic Gaucher disease
Abstract
Gaucher disease (GD) is a lysosomal storage disorder caused by deficient acid β-glucosidase (GCase) activity and consequent accumulation of glucosylceramide. Current enzyme replacement and substrate reduction therapies improve several systemic manifestations but have limited impact on neuronopathic disease, motivating evaluation of alternative molecular strategies. This study computationally assessed the interaction of EPA-phosphatidylcholine (EPA-PC), a marine-derived omega-3 phospholipid, with human GCase (PDB ID: 2NSX). The protein structure was examined by Ramachandran analysis and hydrophobicity profiling, followed by AutoDock Vina engine docking at the proposed hydrophobic i-face. EPA-PC showed a docking score of -5.5 kcal/mol under the applied protocol. Independent PLIP profiling of the docked complex identified predominantly hydrophobic contacts, one hydrogen bond involving Phe347, and Arg395-mediated salt-bridge interactions. A single 200 ns molecular dynamics trajectory of the EPA-PC-GCase complex showed an apparent backbone RMSD plateau of approximately 0.35-0.40 nm and a radius of gyration near 2.4 nm without a sustained increase in global compactness or solvent exposure. These observations support persistence of the modelled complex during the reported trajectory but do not establish ligand-induced GCase stabilisation or pharmacological-chaperone activity. In silico ADMET profiling also indicated substantial liabilities, including very high plasma protein…
Read the paper
Related studies
- eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses
- Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer
- OptiType: precision HLA typing from next-generation sequencing data
- Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications
- Saccharomyces cerevisiae cells have three Omega class glutathione S-transferases acting as 1-Cys thiol transferases
- Hemolysis at low blood flow rates: in-vitro and in-silico evaluation of a centrifugal blood pump
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.