Computational Analysis of GAT1 Mutations: Functional Consequences from Molecular Dynamics and Binding Free Energy Calculations.

ABSTRACT: GABA transporter 1 (GAT1), encoded by the SLC6A1 gene, is essential for maintaining inhibitory neurotransmission by mediating the reuptake of GABA from the synaptic cleft. Dysfunction of GAT1 has been linked to several neurological and neurodevelopmental disorders, including epilepsy and Alzheimer's disease. In this study, we performed a comprehensive computational investigation of reported GAT1 mutations to understand their structural and functional implications. Seven mutations (G63S, Y140C, Q291Δ, F294Δ, N310I, D451G, and G457H) were analyzed using homology modeling, structural validation tools, molecular dynamics (MD) simulation triplicates, and binding free energy calculations via the gmx_MMPBSA method. The wild-type consistently exhibited the most favorable interaction energy

SUBMITTER: Yasir M 

PROVIDER: S-EPMC12692106 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature