Molecular dynamics simulation analysis of water cluster in the ligand-binding pocket of medaka fish taste receptor protein

Abstract Molecular dynamics simulations were performed to investigate the medaka fish taste receptor protein T1r2a-T1r3 complexed with four different amino acid ligands, L-glutamate, L-glutamine, L-alanine, and glycine. We focused on the structure and dynamics of water clusters in the ligand-binding pocket of T1r2a, as previous experimental studies have shown that T1r2a has a higher ligand specificity than T1r3. The simulation revealed that a number of water molecules dynamically formed alternating hydrogen bonds with the α-substituents of the amino acid ligands. The water cluster with the ligands L-glutamine and L-alanine showed similar distance and angle distributions as well as time-correlation functions of the number of hydrogen bonds. As these ligands are known to exhibit higher affinity to the receptor than the others, our results seem to imply that the characteristics of the water cluster in the ligand binding pocket is related to the affinity.