Dissimilar Ligands Bind in a Similar Fashion: A Guide to Ligand Binding-Mode Prediction with Application to CELPP Studies

The molecular similarity principle has achieved great successes in the field of drug design/discovery. Existing studies have focused on similar ligands, while the behaviors of dissimilar ligands remain unknown. In this study, we developed an intercomparison strategy in order to compare the binding m...

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Autores principales:	Xianjin Xu, Xiaoqin Zou
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	molecular similarity principle dissimilar ligand binding-mode prediction protein–ligand interactions drug discovery CELPP Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/2bf7681dd2554fa4ada884b56de0c2d6
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spelling	oai:doaj.org-article:2bf7681dd2554fa4ada884b56de0c2d62021-11-25T17:55:22ZDissimilar Ligands Bind in a Similar Fashion: A Guide to Ligand Binding-Mode Prediction with Application to CELPP Studies10.3390/ijms2222123201422-00671661-6596https://doaj.org/article/2bf7681dd2554fa4ada884b56de0c2d62021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12320https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The molecular similarity principle has achieved great successes in the field of drug design/discovery. Existing studies have focused on similar ligands, while the behaviors of dissimilar ligands remain unknown. In this study, we developed an intercomparison strategy in order to compare the binding modes of ligands with different molecular structures. A systematic analysis of a newly constructed protein–ligand complex structure dataset showed that ligands with similar structures tended to share a similar binding mode, which is consistent with the Molecular Similarity Principle. More importantly, the results revealed that dissimilar ligands can also bind in a similar fashion. This finding may open another avenue for drug discovery. Furthermore, a template-guiding method was introduced for predicting protein–ligand complex structures. With the use of dissimilar ligands as templates, our method significantly outperformed the traditional molecular docking methods. The newly developed template-guiding method was further applied to recent CELPP studies.Xianjin XuXiaoqin ZouMDPI AGarticlemolecular similarity principledissimilar ligandbinding-mode predictionprotein–ligand interactionsdrug discoveryCELPPBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12320, p 12320 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	molecular similarity principle dissimilar ligand binding-mode prediction protein–ligand interactions drug discovery CELPP Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	molecular similarity principle dissimilar ligand binding-mode prediction protein–ligand interactions drug discovery CELPP Biology (General) QH301-705.5 Chemistry QD1-999 Xianjin Xu Xiaoqin Zou Dissimilar Ligands Bind in a Similar Fashion: A Guide to Ligand Binding-Mode Prediction with Application to CELPP Studies
description	The molecular similarity principle has achieved great successes in the field of drug design/discovery. Existing studies have focused on similar ligands, while the behaviors of dissimilar ligands remain unknown. In this study, we developed an intercomparison strategy in order to compare the binding modes of ligands with different molecular structures. A systematic analysis of a newly constructed protein–ligand complex structure dataset showed that ligands with similar structures tended to share a similar binding mode, which is consistent with the Molecular Similarity Principle. More importantly, the results revealed that dissimilar ligands can also bind in a similar fashion. This finding may open another avenue for drug discovery. Furthermore, a template-guiding method was introduced for predicting protein–ligand complex structures. With the use of dissimilar ligands as templates, our method significantly outperformed the traditional molecular docking methods. The newly developed template-guiding method was further applied to recent CELPP studies.
format	article
author	Xianjin Xu Xiaoqin Zou
author_facet	Xianjin Xu Xiaoqin Zou
author_sort	Xianjin Xu
title	Dissimilar Ligands Bind in a Similar Fashion: A Guide to Ligand Binding-Mode Prediction with Application to CELPP Studies
title_short	Dissimilar Ligands Bind in a Similar Fashion: A Guide to Ligand Binding-Mode Prediction with Application to CELPP Studies
title_full	Dissimilar Ligands Bind in a Similar Fashion: A Guide to Ligand Binding-Mode Prediction with Application to CELPP Studies
title_fullStr	Dissimilar Ligands Bind in a Similar Fashion: A Guide to Ligand Binding-Mode Prediction with Application to CELPP Studies
title_full_unstemmed	Dissimilar Ligands Bind in a Similar Fashion: A Guide to Ligand Binding-Mode Prediction with Application to CELPP Studies
title_sort	dissimilar ligands bind in a similar fashion: a guide to ligand binding-mode prediction with application to celpp studies
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2bf7681dd2554fa4ada884b56de0c2d6
work_keys_str_mv	AT xianjinxu dissimilarligandsbindinasimilarfashionaguidetoligandbindingmodepredictionwithapplicationtocelppstudies AT xiaoqinzou dissimilarligandsbindinasimilarfashionaguidetoligandbindingmodepredictionwithapplicationtocelppstudies
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Dissimilar Ligands Bind in a Similar Fashion: A Guide to Ligand Binding-Mode Prediction with Application to CELPP Studies

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