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Computational Methods Used in Hit-to-Lead and Lead Optimization Stages of Structure-Based Drug Discovery

Heifetz, A; Southey, M; Morao, I; Townsend-Nicholson, A; Bodkin, MJ; (2017) Computational Methods Used in Hit-to-Lead and Lead Optimization Stages of Structure-Based Drug Discovery. Methods in Molecular Biology , 1705 pp. 375-394. 10.1007/978-1-4939-7465-8_19. Green open access

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Abstract

GPCR modeling approaches are widely used in the hit-to-lead (H2L) and lead optimization (LO) stages of drug discovery. The aims of these modeling approaches are to predict the 3D structures of the receptor-ligand complexes, to explore the key interactions between the receptor and the ligand and to utilize these insights in the design of new molecules with improved binding, selectivity or other pharmacological properties. In this book chapter, we present a brief survey of key computational approaches integrated with hierarchical GPCR modeling protocol (HGMP) used in hit-to-lead (H2L) and in lead optimization (LO) stages of structure-based drug discovery (SBDD). We outline the differences in modeling strategies used in H2L and LO of SBDD and illustrate how these tools have been applied in three drug discovery projects.

Type: Article
Title: Computational Methods Used in Hit-to-Lead and Lead Optimization Stages of Structure-Based Drug Discovery
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/978-1-4939-7465-8_19
Publisher version: http://dx.doi.org/10.1007/978-1-4939-7465-8_19
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Docking, G protein-coupled receptor, Hit-to-lead, Lead optimization, Molecular dynamics, Simulation, Structure-based drug design
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10043091
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