Computer Simulator of Glycine Receptor Activity: A New Window into a Virtual World

Abstract

Our study reports computer software that simulates the work of a single glycine receptor (GlyR). GlyRs have been found in various types of tissues, but their most important role seems to be in neurons, where they hyperpolarise membranes by opening chloride transmembrane channels. The software is based on a combination of two blocks. One block describes the Brownian dynamics of charged particle motion in a dielectric medium, and the other block determines the probability and timing of receptor activation. Using this software, the voltage–current dependencies and time curves of the transmembrane current were obtained. The mean value of the simulated anion current (4.5 ± 0.3 pA) is in good agreement with measured values under identical conditions ($4.7\pm 0.1$ pA). It was shown that there is a condition under which the GlyR anion channel remains active despite a negligible chloride gradient. Virtual experiments allow evaluation of the value of half maximal effective concentration (EC$_{50}$) of the GlyR ($93\pm 6$ $\upmu$M) and confirm that this receptor activates according to a mechanism involving three ligand binding sites. The advantage of the model is the ability to adjust parameters to the precise demands of experimental researchers. Moreover, the introduced algorithm has low computational power demands; therefore, it can be used as a research tool for assistance with structural experiments and applied aspects of neurophysiology.