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Towards systematic exploration of chemical space: building the fragment library module in molecular property diagnostic suite
A fragment-based drug discovery (FBDD) approach has traditionally been of utmost significance in drug design studies. It allows the exploration of large chemical space to find novel scaffolds and chemotypes which can be improved into selective inhibitors with good affinity. In the current work, seve...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9362107/ https://www.ncbi.nlm.nih.gov/pubmed/35925528 http://dx.doi.org/10.1007/s11030-022-10506-5 |
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author | Gaur, Anamika Singh John, Lijo Kumar, Nandan Vivek, M. Ram Nagamani, Selvaraman Mahanta, Hridoy Jyoti Sastry, G. Narahari |
author_facet | Gaur, Anamika Singh John, Lijo Kumar, Nandan Vivek, M. Ram Nagamani, Selvaraman Mahanta, Hridoy Jyoti Sastry, G. Narahari |
author_sort | Gaur, Anamika Singh |
collection | PubMed |
description | A fragment-based drug discovery (FBDD) approach has traditionally been of utmost significance in drug design studies. It allows the exploration of large chemical space to find novel scaffolds and chemotypes which can be improved into selective inhibitors with good affinity. In the current work, several public domain chemical libraries (ChEMBL, DrugCentral, PDB ligands, COCONUT, and SAVI) comprising bioactive and virtual molecules were retrieved to develop a fragment library. A systematic fragmentation method that breaks a given molecule into rings, linkers, and substituents was used to cleave the molecules and the fragments were analyzed. Further, only the ring framework was taken into the consideration to develop a fragment library that consists of a total number of 107,614 unique fragments. This set represents a rich diverse structure framework that covers a wide variety of yet-to-be-explored fragments for a wide range of small molecule-based applications. This fragment library is an integral part of the molecular property diagnostic suite (MPDS) suite that can be used with other modeling and informatics methods for FBDD approaches. The fragment library module of MPDS can be accessed at http://mpds.neist.res.in:8085. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11030-022-10506-5. |
format | Online Article Text |
id | pubmed-9362107 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-93621072022-08-10 Towards systematic exploration of chemical space: building the fragment library module in molecular property diagnostic suite Gaur, Anamika Singh John, Lijo Kumar, Nandan Vivek, M. Ram Nagamani, Selvaraman Mahanta, Hridoy Jyoti Sastry, G. Narahari Mol Divers Original Article A fragment-based drug discovery (FBDD) approach has traditionally been of utmost significance in drug design studies. It allows the exploration of large chemical space to find novel scaffolds and chemotypes which can be improved into selective inhibitors with good affinity. In the current work, several public domain chemical libraries (ChEMBL, DrugCentral, PDB ligands, COCONUT, and SAVI) comprising bioactive and virtual molecules were retrieved to develop a fragment library. A systematic fragmentation method that breaks a given molecule into rings, linkers, and substituents was used to cleave the molecules and the fragments were analyzed. Further, only the ring framework was taken into the consideration to develop a fragment library that consists of a total number of 107,614 unique fragments. This set represents a rich diverse structure framework that covers a wide variety of yet-to-be-explored fragments for a wide range of small molecule-based applications. This fragment library is an integral part of the molecular property diagnostic suite (MPDS) suite that can be used with other modeling and informatics methods for FBDD approaches. The fragment library module of MPDS can be accessed at http://mpds.neist.res.in:8085. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11030-022-10506-5. Springer International Publishing 2022-08-04 /pmc/articles/PMC9362107/ /pubmed/35925528 http://dx.doi.org/10.1007/s11030-022-10506-5 Text en © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Original Article Gaur, Anamika Singh John, Lijo Kumar, Nandan Vivek, M. Ram Nagamani, Selvaraman Mahanta, Hridoy Jyoti Sastry, G. Narahari Towards systematic exploration of chemical space: building the fragment library module in molecular property diagnostic suite |
title | Towards systematic exploration of chemical space: building the fragment library module in molecular property diagnostic suite |
title_full | Towards systematic exploration of chemical space: building the fragment library module in molecular property diagnostic suite |
title_fullStr | Towards systematic exploration of chemical space: building the fragment library module in molecular property diagnostic suite |
title_full_unstemmed | Towards systematic exploration of chemical space: building the fragment library module in molecular property diagnostic suite |
title_short | Towards systematic exploration of chemical space: building the fragment library module in molecular property diagnostic suite |
title_sort | towards systematic exploration of chemical space: building the fragment library module in molecular property diagnostic suite |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9362107/ https://www.ncbi.nlm.nih.gov/pubmed/35925528 http://dx.doi.org/10.1007/s11030-022-10506-5 |
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