Molecular Simulation of the Diffusion Processes in Membrane Structures on the Examples of the Serotonin Receptor Ion Channel

Studying dynamics and function of ion channels is a field of interest of modern experimental molecular biology. At the same time, there are limited number of methods that allow studying the processes on molecular level with atomic precision. The most accurate methods that provide data on the atomic structure of molecules are the X-ray crystallography (XRC) and the nuclear magnetic resonance spectroscopy (NMR) methods. However, the XRC method provides data on the atomic structure of the crystallized molecule, while the crystallization conditions are usually far from physiological. Using structural data, obtained from the XRC/NMR methods, it is impossible to determine the state of the channel (open or closed) and analyze the dynamic of the processes under study. In this article, the molecular simulation methods are used to study the structure, dynamics and the diffusion processes on the water-membrane interface, as well as the process of ion transportation in 5-HT3 mouse serotonin 5HT-3 receptor, the spatial structure of which was determined in 2014. Based on the full-atom structure of the ion channel, we constructed the model, containing transmembrane domain of the 5-HT3 receptor with lipid bilayer and solvent. Molecular dynamics protocols for simulation of the transmebrane domain of the ion channel were developed. We used steered molecular dynamics for simulation of the transmembrane Na+ ion transport under external electric field. Using the umbrella sampling method, we estimated the free energy profile of Na+ ions transfer through the channel. Using the computer simulation methods (including molecular dynamics method) allowed us making reasonable assumptions about the conformation and conductive state of the ion channel under study.

molecular modelling, molecular dynamics, steered molecular dynamics, diffusion, biomembranes, lipid bilayers, ion channels, serotonin receptor, transmembrane transport, membrane potential

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