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International Journal of Medicinal Chemistry
Volume 2017, Article ID 1529402, 9 pages
Review Article

Biophysical Approaches Facilitate Computational Drug Discovery for ATP-Binding Cassette Proteins

1Faculty of Medicine, University of Toronto, Toronto, ON, Canada
2Department of Chemistry & Biochemistry, College of Arts and Sciences, South Dakota State University, Brookings, SD, USA

Correspondence should be addressed to Saumel Ahmadi; ac.otnorotu.liam@idamha.lemuas

Received 6 January 2017; Accepted 27 February 2017; Published 19 March 2017

Academic Editor: Vassilios Myrianthopoulos

Copyright © 2017 Steven V. Molinski et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Although membrane proteins represent most therapeutically relevant drug targets, the availability of atomic resolution structures for this class of proteins has been limited. Structural characterization has been hampered by the biophysical nature of these polytopic transporters, receptors, and channels, and recent innovations to in vitro techniques aim to mitigate these challenges. One such class of membrane proteins, the ATP-binding cassette (ABC) superfamily, are broadly expressed throughout the human body, required for normal physiology and disease-causing when mutated, yet lacks sufficient structural representation in the Protein Data Bank. However, recent improvements to biophysical techniques (e.g., cryo-electron microscopy) have allowed for previously “hard-to-study” ABC proteins to be characterized at high resolution, providing insight into molecular mechanisms-of-action as well as revealing novel druggable sites for therapy design. These new advances provide ample opportunity for computational methods (e.g., virtual screening, molecular dynamics simulations, and structure-based drug design) to catalyze the discovery of novel small molecule therapeutics that can be easily translated from computer to bench and subsequently to the patient’s bedside. In this review, we explore the utility of recent advances in biophysical methods coupled with well-established in silico techniques towards drug development for diseases caused by dysfunctional ABC proteins.