Gillet, V. orcid.org/0000-0002-8403-3111, Seddon, M.P. and Cosgrove, D.A. (2018) Bioisosteric replacements extracted from high quality structures in the protein databank. ChemMedChem, 13 (6). pp. 607-613. ISSN 1860-7179
Abstract
Bioisosterism is an important concept in the lead optimization phase of drug discovery where the aim is to make modifications to parts of a molecule with the aim of improving some properties while maintaining others. We present an analysis of bioisosteric fragments extracted from the ligands in an established data set consisting of 121 protein targets. A pairwise analysis is carried out of all ligands for a given target. The ligands are fragmented using the BRICS fragmentation scheme and a pair of fragments is deemed to be bioisosteric if they occupy a similar volume of the protein binding site. We consider two levels of generality, one which does not consider the number of attachment points in the fragments and a more restricted case in which both fragments are required to have the same number of attachments. We investigate the extent to which the bioisosteric pairs that are found are common across different target.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an author-produced version of a paper subsequently published in ChemMedChem. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | bioisosteres; fragmentation; molecular overlay; pharmacophore |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Social Sciences (Sheffield) > Information School (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 22 Jan 2018 12:43 |
Last Modified: | 11 Nov 2020 11:38 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/cmdc.201700679 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:126476 |