IFIBIO HOUSSAY   25014
INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
EFFECT OF MEMBRANE COMPOSITION ON EPITHELIAL SODIUM CHANNEL (ENAC) AND AQUAPORIN 1 (AQP1) FUNCTION. ALL-ATOM AND COARSE-GRAINED MOLECULAR DYNAMICS APPROACH
Autor/es:
RICARDO A. DORR; ROXANA TORIANO; JUAN JOSÉ CASAL
Reunión:
Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020
Resumen:
ENaC is a major regulator of salt and water reabsorption in several epithelial tissues. AQP1 is a membrane integral protein with key role in transcellular water transport in response to osmotic gradients. Both proteins are present in vascular endothelial cells but their functions in this tissue would not be related to their canonical functions. Our in vitro experimental results strongly suggest that there is a relationship between them. The characterization of lipid-lipid, lipid-protein and protein-protein interactions is a key factor in understanding the modulation effects that membrane lipids and proteins can have on each other. Using molecular dynamics simulations (MDS) as a ?computational microscope? we can characterize the interactions of membrane proteins with lipids, matching, incorporating, and extending the information which may be obtained from experimental, structural and biophysical studies. Homology modeling of ENaC was carried out with the Uniprot sequence (P37088, P51168, P51170) with 6BQN as template on the Swiss-Model server. Subsequent refinement was carried out through MDS. The system consisted of a lipid bilayer ofPOPC:DOPC:DPPC:CHOL at different relative concentrations, the AQP1 tetramer (PDB code 4CSK) and the modeled ENaC, in the presence of TIP3P type water molecules. It was prepared usingthe CHARMM-GUI Web-based graphical interface and CHARMM36 force field. The MDS were performed with GROMACS 2019 package and GROMACS tools were used for analysis of the following bilayer properties: the surface area per lipid, compressibility modulus, mass density profile, two-dimensional density maps of lipid distribution and lateral diffusion coefficients. The bilayers properties were used to correlate the permeability of ENaC and AQP1 on electrophysiology models with the GROMACS package. Additional studies involved the molecular docking technique to analyze the possible binding modes of aldosterone with ENaC and its influence on channel functionality.