Title
Biophysical Approaches Facilitate Computational Drug Discovery for ATP-Binding Cassette Proteins
Document Type
Article
Publication Date
2017
Abstract
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.
Publication Title
International Journal of Medicinal Chemistry
Volume
2017
Issue
Article ID 1529402
Format
application/pdf
Language
en
DOI of Published Version
10.1155/2017/1529402
Publisher
Hindawi
Rights
Copyright © 2017 The Authors
Recommended Citation
Molinski, Steven V.; Bozoky, Zoltan; Iram, Surtaj H.; and Ahmadi, Saumel, "Biophysical Approaches Facilitate Computational Drug Discovery for ATP-Binding Cassette Proteins" (2017). Chemistry and Biochemistry Faculty Publications. 31.
https://openprairie.sdstate.edu/chem_pubs/31
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.