In-silico Analysis of the Molecular Interactions between ICAM-1 and MIC2 for the Exploration of the Transepithelial migration of Toxoplasma gondii into Host Cells

Abstract

Toxoplasmosis is a medically significant zoonosis that may be contracted from the fecal matter of infected cats. Elucidating protein-protein interactions (PPIs) is essential in assessing the functions of mechanisms in cells, particularly in their metabolic reactions and in molecular transport from one location to another. Elucidation of Toxoplasma gondii PPI networks of differentially expressed genes (DEGs) contributed to existing information on gene and protein functional annotation, pathway annotation, and gene enrichment analyses. This study was conducted to determine the protein interactions present in the binding of human ICAM-1 to the parasite adhesin MIC2 using a coarse-grained molecular dynamics (CGMD) simulation to determine how these lead to the transepithelial migration of Toxoplasma gondii into host cells. This CGMD was simulated on the GROMACS Software Package 2018. The ICAM-1-MIC2-membrane system, including the water, ion species, and coarse-grained beads, were modeled using the Martini 22 CG Force Field Parameters applying three-dimensional boundary conditions, over a simulation time of 3 microseconds. Our results show that T. gondii utilizes MIC2 as a vessel to attach to the cell membrane through ICAM-1. These interactions between ICAM-1 and MIC2 allow for T. gondii entry into the host cell as evidenced by increased contact, with a Root Mean Square Fluctuation (RMSF) ratio of 0.513 for the average number of contacts from 0 to 1500 ns, and and RMSF ratio of 0.129 for the average number of contacts from 1500 to 3000 ns. The relative RMSF ratio from 1500 to 3000 ns is lower compared to the relative RMSF ratio from 0 to 1500 ns, which indicates stabilized molecular fluctuations over time.