Journal
ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 18
Volume 18, Issue -, Pages 51-76Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-bioeng-092115-025322
Keywords
transmembrane domains; drug discovery; high-throughput screening; rational design; curvature sensing
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Funding
- NIGMS NIH HHS [R01 GM103843, R01 GM101279, T32 GM142607, T32 GM008759] Funding Source: Medline
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008759, R01GM103843, R01GM101279] Funding Source: NIH RePORTER
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The majority of therapeutics target membrane proteins, accessible on the surface of cells, to alter cellular signaling. Cells use membrane proteins to transduce signals into cells, transport ions and molecules, bind cells to a surface or substrate, and catalyze reactions. Newly devised technologies allow us to drug conventionally undruggable regions of membrane proteins, enabling modulation of protein-protein, protein-lipid, and protein-nucleic acid interactions. In this review, we survey the state of the art of high-throughput screening and rational design in drug discovery, and we evaluate the advances in biological understanding and technological capacity that will drive pharmacotherapy forward against unorthodox membrane protein targets.
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