Docking, qm/mm, and molecular dynamics simulations of the hexose transporter from plasmodium falciparum (pfht)

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dc.creatorAmanda Luisa da Fonseca
dc.creatorRenata Rachide Nunes
dc.creatorVanildo Martins Lima Braga
dc.creatorMoacyr Comar Jr
dc.creatorRicardo José Alves
dc.creatorFernando de Pilla Varotti
dc.creatorAlex Gutterres Taranto
dc.date.accessioned2022-05-09T19:09:09Z
dc.date.accessioned2025-09-09T01:11:33Z
dc.date.available2022-05-09T19:09:09Z
dc.date.issued2016-05
dc.identifier.doihttp://dx.doi.org/10.1016/j.jmgm.2016.03.015
dc.identifier.issn1093-3263
dc.identifier.urihttps://hdl.handle.net/1843/41482
dc.languagepor
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofJournal of Molecular Graphics and Modelling
dc.rightsAcesso Restrito
dc.subjectGlicose
dc.subjectMalária
dc.subject.otherComparative homology modeling
dc.subject.otherComputer aided drug-design (CADD)
dc.subject.otherGlucose transport
dc.subject.otherMalaria
dc.subject.otherPfHT
dc.subject.otherQM/MM
dc.titleDocking, qm/mm, and molecular dynamics simulations of the hexose transporter from plasmodium falciparum (pfht)
dc.typeArtigo de periódico
local.citation.epage186
local.citation.spage174
local.citation.volume66
local.description.resumoMalaria is the most prevalent parasitic disease in the world. Currently, an effective vaccine for malaria does not exist, and chemotherapy must be used to treat the disease. Because of increasing resistance to current antimalarial drugs, new treatments must be developed. Among the many potential molecular targets, the hexose transporter of Plasmodium falciparum (PfHT) is particularly promising because it plays a vital role in glucose transport for the parasite. Thus, this study aims to determine the three-dimensional structure of PfHT and to describe the intermolecular interactions between active glycoside derivatives and PfHT. Such information should aid in the development of new antimalarial drugs. The receptor PfHT was constructed from primary sequences deposited in the SWISS MODEL database. Next, molecular docking simulations between O-(undec-10-en)-l-D-glucose and the constructed active site models were performed using Autodock Vina. The glycoside derivative-PfHT complexes were then refined using the hybrid QM/MM (PM3/ff03) method within the AMBER package. The models were then evaluated using Ramachandran plots, which indicated that 93.2% of the residues in the refined PfHT models (P5) were present in favorable regions. Furthermore, graphical plots using ANOLEA showed that the potential energies of interaction for atoms unbonded to P5 were negative. Finally, the O-(undec-10-en)-l-D-glucose-PfHT complex was eval- uated using 20-ns Molecular Dynamics simulations with an ff03 force field. Docking and QM/MM studies revealed the amino acids essential for molecular recognition of and activity on glycosides. Inhibition of glucose transporters may prevent the development and metabolism of P. falciparum, so a description of the receptor’s structure is a critical step towards rational drug design.
local.publisher.countryBrasil
local.publisher.departmentFAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S1093326316300493

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