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Genomes, structural biology and drug discovery: combating the impacts of mutations in genetic disease and antibiotic resistance

Published version
Peer-reviewed

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Authors

Pandurangan, AP 
Ascher, DB 
Thomas, SE 
Blundell, TL 

Abstract

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.

Description

Keywords

structure-guided drug discovery, mutational analysis, genetic disease, antimicrobial resistance

Journal Title

Biochemical Society Transactions

Conference Name

Journal ISSN

0300-5127
1470-8752

Volume Title

45

Publisher

Portland Press
Sponsorship
Medical Research Council (MR/M026302/1)
Medical Research Council (MR/N501864/1)
Wellcome Trust (093167/Z/10/Z)
European Commission (260872)
European Commission (40196)
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.