Human lactate dehydrogenase a inhibitors: a molecular dynamics investigation.

Lactate dehydrogenase A (LDHA) is an important enzyme in fermentative glycolysis, generating most energy for cancer cells that rely on anaerobic respiration even under normal oxygen concentrations. This renders LDHA a promising molecular target for the treatment of various cancers. Several efforts h...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yun Shi, B Mario Pinto
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/abca69299a7246b0a79a3495c68266eb
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:abca69299a7246b0a79a3495c68266eb
record_format	dspace
spelling	oai:doaj.org-article:abca69299a7246b0a79a3495c68266eb2021-11-18T08:37:23ZHuman lactate dehydrogenase a inhibitors: a molecular dynamics investigation.1932-620310.1371/journal.pone.0086365https://doaj.org/article/abca69299a7246b0a79a3495c68266eb2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24466056/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Lactate dehydrogenase A (LDHA) is an important enzyme in fermentative glycolysis, generating most energy for cancer cells that rely on anaerobic respiration even under normal oxygen concentrations. This renders LDHA a promising molecular target for the treatment of various cancers. Several efforts have been made recently to develop LDHA inhibitors with nanomolar inhibition and cellular activity, some of which have been studied in complex with the enzyme by X-ray crystallography. In this work, we present a molecular dynamics (MD) study of the binding interactions of selected ligands with human LDHA. Conventional MD simulations demonstrate different binding dynamics of inhibitors with similar binding affinities, whereas steered MD simulations yield discrimination of selected LDHA inhibitors with qualitative correlation between the in silico unbinding difficulty and the experimental binding strength. Further, our results have been used to clarify ambiguities in the binding modes of two well-known LDHA inhibitors.Yun ShiB Mario PintoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e86365 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yun Shi B Mario Pinto Human lactate dehydrogenase a inhibitors: a molecular dynamics investigation.
description	Lactate dehydrogenase A (LDHA) is an important enzyme in fermentative glycolysis, generating most energy for cancer cells that rely on anaerobic respiration even under normal oxygen concentrations. This renders LDHA a promising molecular target for the treatment of various cancers. Several efforts have been made recently to develop LDHA inhibitors with nanomolar inhibition and cellular activity, some of which have been studied in complex with the enzyme by X-ray crystallography. In this work, we present a molecular dynamics (MD) study of the binding interactions of selected ligands with human LDHA. Conventional MD simulations demonstrate different binding dynamics of inhibitors with similar binding affinities, whereas steered MD simulations yield discrimination of selected LDHA inhibitors with qualitative correlation between the in silico unbinding difficulty and the experimental binding strength. Further, our results have been used to clarify ambiguities in the binding modes of two well-known LDHA inhibitors.
format	article
author	Yun Shi B Mario Pinto
author_facet	Yun Shi B Mario Pinto
author_sort	Yun Shi
title	Human lactate dehydrogenase a inhibitors: a molecular dynamics investigation.
title_short	Human lactate dehydrogenase a inhibitors: a molecular dynamics investigation.
title_full	Human lactate dehydrogenase a inhibitors: a molecular dynamics investigation.
title_fullStr	Human lactate dehydrogenase a inhibitors: a molecular dynamics investigation.
title_full_unstemmed	Human lactate dehydrogenase a inhibitors: a molecular dynamics investigation.
title_sort	human lactate dehydrogenase a inhibitors: a molecular dynamics investigation.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/abca69299a7246b0a79a3495c68266eb
work_keys_str_mv	AT yunshi humanlactatedehydrogenaseainhibitorsamoleculardynamicsinvestigation AT bmariopinto humanlactatedehydrogenaseainhibitorsamoleculardynamicsinvestigation
_version_	1718421580385615872

Human lactate dehydrogenase a inhibitors: a molecular dynamics investigation.

Ejemplares similares