Molecular dynamics simulations of PfAQP from the malarial parasite Plasmodium falciparum

Abstract

Aquaporins (AQPs) are widely distributed in all kingdoms of life and act as facilitators in the transport of water and other small solutes through cell membranes. Since the plasmodial and human AQPs are different in their primary and secondary structure, an intervention targeting plasmodial AQP without affecting human AQPs is discussed to identify an attractive novel target against malaria. Therefore, it is crucial to understand the action mechanisms of these plasmodial AQPs. To explore the progression of the plasmodial real AQPs in vivo at work, a molecular dynamic simulation system was successfully developed for a PfAQP tetramer in silico. The results showed that the transporting work was not synchronous in the four channels at the same time, and that it was different at different times in the same channel. The hole sizes varied in different channels with time. The structure analysis showed that both hydrophobic and hydrophilic residues composed the inner surface of the channels, and the asparagines Asn-193 and Asn-70 assembled into two motifs of NLA and NPS in the center of the channel in place of the signature motifs of NPA in other AQPs. In brief, we successfully developed an equilibrated PfAQP-lipid system by molecular dynamics simulations, and investigated the structure of the PfAQP channel, which should aid our understanding of the AQP structure and its functional implications.

Partners in Mischief: Functional Networks of Heat Shock Proteins of Plasmodium falciparum and Their Influence on Parasite Virulence

“…Also, in blood stages, inhibition of Hsp90 function blocks ring to trophozoite transition at a point where the parasite is ramping up its protein synthesis [56]. Furthermore, recent studies have revealed that parasite Hsp70s are upregulated in artemisinin-resistant parasites, and that the Hsp70 locus is found in an area of positive selection pressure related to this resistance phenotype [112,113]. It remains however unclear if Hsp70 has a direct influence on arteminisin tolerance, or whether upregulation is part of a general stress response, possibly initiated by the supposed oxidative stress associated with artemisinin exposure [109].…”

Molecular Dynamics Simulations of Mite Aquaporin DerfAQP1 from the Dust Mite Dermatophagoides farinae (Acariformes: Pyroglyphidae)

“…Molecular dynamics simulations (MDS) can go beyond static structures, thus offering an ideal method to understand the working mechanism of water and glycerol transport through AQPs at atomic resolution. On the basis of our reports on human AQP4 [8], PfAQP from the malarial parasite Plasmodium falciparum [9], and Aqy1 from Pichia pastoris [10], the setup for these simulations typically involves a box containing the protein embedded in a simple membrane surrounded with water.…”