Ligand- and Structure-based Approaches for Transmembrane Transporter Modeling

Author(s)

Melanie Grandits, Gerhard F Ecker

Abstract

The study of transporter proteins is key to understanding the mechanism behind multi-drug resistance and drug-drug interactions causing severe side effects. While ATP-binding transporters are well-studied, solute carriers illustrate an understudied family with a high number of orphan proteins. To study these transporters, in silico methods can be used to shed light on the basic molecular machinery by studying protein-ligand interactions. Nowadays, computational methods are an integral part of the drug discovery and development process. In this short review, computational approaches, such as machine learning, are discussed, which try to tackle interactions between transport proteins and certain compounds to locate target proteins. Furthermore, a few cases of selected members of the ATP binding transporter and solute carrier family are covered, which are of high interest in clinical drug interaction studies, especially for regulatory agencies. The strengths and limitations of ligand-based and structure-based methods are discussed to highlight their applicability for different studies. Furthermore, the combination of multiple approaches can improve the information obtained to find crucial amino acids that explain important interactions of protein-ligand complexes in more detail. This allows the design of drug candidates with increased activity towards a target protein, which further helps to support future synthetic efforts.

Organisation(s)

Department of Pharmaceutical Sciences

Journal

Current drug research reviews

ISSN

2589-9775

DOI

https://doi.org/10.2174/2589977515666230508123041

Publication date

2023

Peer reviewed

Yes

Austrian Fields of Science 2012

301207 Pharmaceutical chemistry

Portal url

https://ucris.univie.ac.at/portal/en/publications/ligand-and-structurebased-approaches-for-transmembrane-transporter-modeling(fca57bcb-1df0-4cb2-9006-6cf756ea9d6c).html