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  • Poster presentation
  • Open Access

Pairwise structural comparison of tiagabine analogs gives new insights into their protein binding modes

  • 1Email author,
  • 1,
  • 2 and
  • 1
Journal of Cheminformatics20135 (Suppl 1) :P32

  • Published:


  • Structural Feature
  • Molecular Modeling
  • Binding Mode
  • Molecular Attribute
  • Linker Region

Tiagabine (Gabitril®) is a selective inhibitor of the human gamma-aminobutyric acid (GABA) transporter 1 (hGAT-1), a transport protein belonging to the family of neurotransmitter-sodium-symporters (NSS). It is a marketed drug, used for treatment of epilepsy. However, the molecular basis of protein-ligand interaction remains obscure due to the lack of a 3D structure of the target protein.

In order to identify activity-determining structural features of a series of tiagabine analogs taken from literature [13], we chose an approach combining traditional methods of molecular modeling with exhaustive sampling of docking poses, and a pairwise comparison of structural features and their respective bioactivity values.

We determined a common binding mode of tiagabine analogs, which is in nice agreement with literature [4]. Further, we were able to trace back considerable differences in inhibitory activities to distinct molecular attributes of the analogs.

Our study revealed the molecular explanation for the importance of a polar linker region and thus paves the way for subsequent screening efforts in the search for novel GAT-1 inhibitors.

Authors’ Affiliations

Department of Medicinal Chemistry, University of Vienna, Althanstrasse 14, Vienna, A-1090, Austria
Medical University of Vienna, Institute of Pharmacology, Vienna, A-1090, Austria


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