Current Advances in Studying Clinically Relevant Transporters of the Solute Carrier (SLC) Family by Connecting Computational Modeling and Data Science

Author(s)
Alžběta Türková, Barbara Zdrazil
Abstract

Organic anion and cation transporting proteins (OATs, OATPs, and OCTs), as well as the Multidrug and Toxin Extrusion (MATE) transporters of the Solute Carrier (SLC) family are playing a pivotal role in the discovery and development of new drugs due to their involvement in drug disposition, drug-drug interactions, adverse drug effects and related toxicity. Computational methods to understand and predict clinically relevant transporter interactions can provide useful guidance at early stages in drug discovery and design, especially if they include contemporary data science approaches. In this review, we summarize the current state-of-the-art of computational approaches for exploring ligand interactions and selectivity for these drug (uptake) transporters. The computational methods discussed here by highlighting interesting examples from the current literature are ranging from semiautomatic data mining and integration, to ligand-based methods (such as quantitative structure-activity relationships, and combinatorial pharmacophore modeling), and finally structure-based methods (such as comparative modeling, molecular docking, and molecular dynamics simulations). We are focusing on promising computational techniques such as fold-recognition methods, proteochemometric modeling or techniques for enhanced sampling of protein conformations used in the context of these ADMET-relevant SLC transporters with a special focus on methods useful for studying ligand selectivity.

Organisation(s)
Department of Pharmaceutical Chemistry
Journal
Computational and Structural Biotechnology Journal
Volume
17
Pages
390-405
No. of pages
16
ISSN
2001-0370
DOI
https://doi.org/10.1016/j.csbj.2019.03.002
Publication date
03-2019
Peer reviewed
Yes
Austrian Fields of Science 2012
Pharmaceutical chemistry, Toxicology, Computer aided design (CAD)
Keywords
ASJC Scopus subject areas
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Portal url
https://ucris.univie.ac.at/portal/en/publications/current-advances-in-studying-clinically-relevant-transporters-of-the-solute-carrier-slc-family-by-connecting-computational-modeling-and-data-science(6ac91816-7933-489a-aaab-379af6e12b95).html