INFLUENCE OF MEMBRANE LIPID COMPOSITION ON WATER DIFFUSION THROUGH HUMAN AQUAPORIN-1

CASAL, JUAN J.; DORR, RICARDO A.; TORIANO, ROXANA

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

Introduction. Lipids play important modulatory and structural roles for membrane proteins. Molecular dynamics simulations (MDS) are frequently used to provide insights into the nature of these protein-lipid interactions. We study the influence of the lipid environment on human Aquaporin-1 (hAQP1, PDB code: 4CSK). Two heterogeneous lipid bilayers, representative of mammals (M) and cancer cells (C), and other only with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), were generated around 4CSK. Methods. CHARMM-GUI was used for the generation of the three systems. 4CSK was embed- ded into a 70 × 70 Å lipid bilayer, with TIP3P water molecule model, neutralizing ions, and a temperature set at 37oC. The CHARMM36m force field was used at production dynamics of 500 ns. GROMACS, VMD and MDAnalysis were used to evaluate the convergence of the simulation, pore radius profile and water diffusion through the protein channels, distances between selectivity residues (ar/R) and the number of water molecules near them and pore length in the narrow zone. Comparative mean, SD and ANOVA tests were used in statistics. Results. Constriction in the ar/R site: varied from a narrow to a wide conformation. A closed state coincides with the absence of water molecules at the site. Water diffusion through protein in DPPC: 8.3 (0.04), C: 8.62 (0.08) > M: 4.44 (0.01), units: 10-14 cm3s- 1. Pore length in C: 20.40 (0.48) > DPPC: 18.94 (0.42) > M: 18.49 (0.37), units: Å. Conclusion. We present quantitative evidence that membrane composition affects AQP1 water dynamics. Our findings confirm the need for further progress in the study of the regulation of aquaporins by their lipid environment. With the emergence of more powerful hardware and advanced simulation techniques and algo- rithms, we can expect an even larger impact of simulations on our understanding of biological membranes and the role of lipids.