Investigating the olfactory function of microplusin-like proteins in Rhipicephalus microplus through molecular...

Ticks are responsible for transmitting infectious pathogens of public health and veterinary importance worldwide. Chemosensory perception in ticks constitutes a fundamental pathway in host location and disease transmission. This study aims to analyze the function of the Rhipicephalus microplus microplusin-like protein (MLP) in the perception of volatile organic compounds. To obtain the results, AlphaFold2, Swiss Model, and AlphaFold3 were utilized for protein prediction. UCSF Chimera, AutoDock Vina in Linux, and Discovery Studio Visualizer were employed for docking analyses and interaction visualizations. The GROMACS software in a virtual Linux environment was used for molecular dynamics simulations. Out of 46 volatile molecules selected based on literature and used for docking, the four top compounds were evaluated for their interaction, including squalene with a binding energy of -5.183 kcal/mol, uric acid with -5.169 kcal/mol, beta-ionone with -5.037 kcal/mol, and 2,4-Di-tert-butylphenol with -5.035 kcal/mol. The stability of MLP with the top two compounds, squalene and uric acid, was evaluated through molecular dynamics simulations. The uric acid complex was more stable. It showed lower and more stable root-mean-square deviation (∼2 nm), as well as hydrogen bonding (2-4 bonds), smoother solvent-accessible surface area, and gyration radius profiles. In contrast, the squalene complex showed greater conformational variability, lacking hydrogen bonding. The Gibbs free energy landscape and principal component analysis revealed that squalene had stabilization at the start of the simulation. In contrast, uric acid showed stronger long-term conformational convergence and stabilization by the end of the simulation. This study demonstrated the potential role of microplusin-like protein in recognizing volatile organic compounds. It provides insights into the potential to develop new tick-control strategies.