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Type:	Artigo de Periódico
Title:	Docking, qm/mm, and molecular dynamics simulations of the hexose transporter from plasmodium falciparum (pfht)
Authors:	Amanda Luisa da Fonseca Renata Rachide Nunes Vanildo Martins Lima Braga Moacyr Comar Jr Ricardo José Alves Fernando de Pilla Varotti Alex Gutterres Taranto
Abstract:	Malaria 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.
Subject:	Glicose Malária
language:	por
metadata.dc.publisher.country:	Brasil
Publisher:	Universidade Federal de Minas Gerais
Publisher Initials:	UFMG
metadata.dc.publisher.department:	FAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS
Rights:	Acesso Restrito
metadata.dc.identifier.doi:	http://dx.doi.org/10.1016/j.jmgm.2016.03.015
URI:	http://hdl.handle.net/1843/41482
Issue Date:	May-2016
metadata.dc.url.externa:	https://www.sciencedirect.com/science/article/pii/S1093326316300493
metadata.dc.relation.ispartof:	Journal of Molecular Graphics and Modelling
Appears in Collections:	Artigo de Periódico

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