Combination of consensus and ensemble docking strategies for the discovery of human dihydroorotate dehydrogenase inhibitors

Abstract The inconsistencies in the performance of the virtual screening (VS) process, depending on the used software and structural conformation of the protein, is a challenging issue in the drug design and discovery field. Varying performance, especially in terms of early recognition of the potent...

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Autores principales:	Garri Chilingaryan, Narek Abelyan, Arsen Sargsyan, Karen Nazaryan, Andre Serobian, Hovakim Zakaryan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/723fa34d85bd42ff9cba9172a8c7d336
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spelling	oai:doaj.org-article:723fa34d85bd42ff9cba9172a8c7d3362021-12-02T15:56:57ZCombination of consensus and ensemble docking strategies for the discovery of human dihydroorotate dehydrogenase inhibitors10.1038/s41598-021-91069-72045-2322https://doaj.org/article/723fa34d85bd42ff9cba9172a8c7d3362021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91069-7https://doaj.org/toc/2045-2322Abstract The inconsistencies in the performance of the virtual screening (VS) process, depending on the used software and structural conformation of the protein, is a challenging issue in the drug design and discovery field. Varying performance, especially in terms of early recognition of the potential hit compounds, negatively affects the whole process and leads to unnecessary waste of the time and resources. Appropriate application of the ensemble docking and consensus-scoring approaches can significantly increase reliability of the VS results. Dihydroorotate dehydrogenase (DHODH) is a key enzyme in the pyrimidine biosynthesis pathway. It is considered as a valuable therapeutic target in cancer, autoimmune and viral diseases. Based on the conducted benchmark study and analysis of the effect of different combinations of the applied methods and approaches, here we suggested a structure-based virtual screening (SBVS) workflow that can be used to increase the reliability of VS.Garri ChilingaryanNarek AbelyanArsen SargsyanKaren NazaryanAndre SerobianHovakim ZakaryanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Garri Chilingaryan Narek Abelyan Arsen Sargsyan Karen Nazaryan Andre Serobian Hovakim Zakaryan Combination of consensus and ensemble docking strategies for the discovery of human dihydroorotate dehydrogenase inhibitors
description	Abstract The inconsistencies in the performance of the virtual screening (VS) process, depending on the used software and structural conformation of the protein, is a challenging issue in the drug design and discovery field. Varying performance, especially in terms of early recognition of the potential hit compounds, negatively affects the whole process and leads to unnecessary waste of the time and resources. Appropriate application of the ensemble docking and consensus-scoring approaches can significantly increase reliability of the VS results. Dihydroorotate dehydrogenase (DHODH) is a key enzyme in the pyrimidine biosynthesis pathway. It is considered as a valuable therapeutic target in cancer, autoimmune and viral diseases. Based on the conducted benchmark study and analysis of the effect of different combinations of the applied methods and approaches, here we suggested a structure-based virtual screening (SBVS) workflow that can be used to increase the reliability of VS.
format	article
author	Garri Chilingaryan Narek Abelyan Arsen Sargsyan Karen Nazaryan Andre Serobian Hovakim Zakaryan
author_facet	Garri Chilingaryan Narek Abelyan Arsen Sargsyan Karen Nazaryan Andre Serobian Hovakim Zakaryan
author_sort	Garri Chilingaryan
title	Combination of consensus and ensemble docking strategies for the discovery of human dihydroorotate dehydrogenase inhibitors
title_short	Combination of consensus and ensemble docking strategies for the discovery of human dihydroorotate dehydrogenase inhibitors
title_full	Combination of consensus and ensemble docking strategies for the discovery of human dihydroorotate dehydrogenase inhibitors
title_fullStr	Combination of consensus and ensemble docking strategies for the discovery of human dihydroorotate dehydrogenase inhibitors
title_full_unstemmed	Combination of consensus and ensemble docking strategies for the discovery of human dihydroorotate dehydrogenase inhibitors
title_sort	combination of consensus and ensemble docking strategies for the discovery of human dihydroorotate dehydrogenase inhibitors
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/723fa34d85bd42ff9cba9172a8c7d336
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Combination of consensus and ensemble docking strategies for the discovery of human dihydroorotate dehydrogenase inhibitors

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