Genomes, structural biology and drug discovery: combating the impacts of mutations in genetic disease and antibiotic resistance
Biochemical Society Transactions
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Pandurangan, A., Ascher, D., Thomas, S., & Blundell, T. (2017). Genomes, structural biology and drug discovery: combating the impacts of mutations in genetic disease and antibiotic resistance. Biochemical Society Transactions, 45 (2), 303-311. https://doi.org/10.1042/BST20160422
For over four decades structural biology has been used to understand the mechanisms of disease, and structure-guided approaches have demonstrated clearly that they can contribute to many aspects of early drug discovery, both computationally and experimentally. Structure can also inform our understanding of impacts of mutations in human genetic diseases and drug resistance in cancers and infectious diseases. We discuss the ways that structural insights might be useful in both repurposing off-licence drugs and guide the design of new molecules that might be less susceptible to drug resistance in the future.
structure-guided drug discovery, mutational analysis, genetic disease, antimicrobial resistance
D.B.A. and T.L.B. are supported by the Wellcome Trust Programme Grant [093167/Z/10/Z]. A.P.P. and T.L.B. have been supported by the Gates HIT-TB and the EU MM4TB [Project ID: 260872] programmes. S.E.T. and T.L.B. are supported by Cystic Fibrosis Trust (Registered as a charity in England and Wales (1079049) and in Scotland (SC040196). Tom L. Blundell was awarded the Biochemical Society Award in 2013; this review is based on the work for which he won the Award.
Wellcome Trust (093167/Z/10/Z)
EC FP7 CP (260872)
European Commission (40196)
Medical Research Council (MR/N501864/1)
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External DOI: https://doi.org/10.1042/BST20160422
This record's URL: https://www.repository.cam.ac.uk/handle/1810/263197