Analysis of alfa helices, extracellular loops and pore region in human aquaporin-1 by molecular dynamics

R. TORIANO; ROSI, PABLO; DORR R

San Miguel de Tucuman

Congreso; III Latin American Federation of Biophysical Societies (LAFeBS) - IX IberoAmerican Congress of Biophysics - XLV Reunión Anual SAB 2016; 2016

Sociedad Argentina de Biofísica

Analysis of α helices, extracellular loops and pore region in human aquaporin-1 by molecular dynamicsRosi Pablo2, Dorr Ricardo1, Camara Amanda3, Toriano Roxana11 Laboratorio de Biomembranas, IFIBIO " Houssay" - CONICET- UBA.2 Laboratorio de Síntesis Inorgánica Avanzada. Departamento de Química Inorgánica, Analítica y Química Física. FCEyN, UBA.3 Instituto de Física de Sao Carlos, USP, Brasil.Human aquaporin-1 (hAQP1) is an integral membrane protein that transports water. In previous work, we demonstrated that the permeability of hAQP1 is modulated by the tension of the plasma membrane. To investigate whether that modulation is related to the dynamic conformation of the pore, the extracellular loops and/or the bending of α helices, the information of two crystalline hAQP1 structures (1FQY and 4CSK) was used. We carried out molecular dynamics (MD) in three different conditions: a) tetramer with restriction in those α-carbons (Cα) that would be in contact with the lipid bilayer (TR); b) tetramer without any further restrictions that those provided by the tetramerization itself (TL); and c) unrestricted monomer (ML). Several descriptors were used for analysis, such as RMSD, the number of water molecules in the pore, modifications in estimated diameter along pore sections, the Solvent Accessible Surface Area (SASA) in residues of the NPA and ar/R sites, the geometry of helices and loops, harmonic analysis using Fourier transform and radial distribution function (g(r)) of water molecules measured in residues influenced by movements of loop A. Principal Component Analysis (PCA) was performed. The results observed were: 1) the contribution of restricting Cα differs from the contribution of tetramerization itself; 2) the tetramerization does not prevent displacement of hydrophilic loops to regions that would not be accessible in the presence of the lipid bilayer; 3) individual monomers behave differently within TL and TR; 4) At level of the pore, no descriptor per se explains the differences observed between TL and TR; 5) localized restrictions in TR cause modifications in far and not restricted sites inside the pore; 6) the distinct behavior shown by H1, H3 and H6 helices becomes the subject of future studies, in search for a possible sensor of the membrane tension that could influence the permeability of the pore.