Unravelling the Weak Interactions in Binary Clusters of Serotonin and Amino Acid Residues

As a monoamine neurotransmitter, serotonin affects a wide range of physiological and behavioral procedures of humans but its biological function is complex and multifaceted. Here we present a comprehensive study of the weak serotonin-residue interactions from cluster science point of view. Eight pairs of serotonin-residue binary clusters are representatively studied. Upon the most stable structures we depict the hydrogen bonding interaction patterns, along with natural bond orbital (NBO) analysis, atoms in molecules (AIM) analysis, generalized Kohn-Sham energy decomposition analysis (GKS-EDA), as well as noncovalent interaction plots based on independent gradient model (IGM). It is found that, for nitrogenous residues, the NH-O dominates the noncovalent interactions; while for hydroxyl-containing residues, O-HN takes over the dominant interactions; for oxygen and nitrogen-free residues, both electrostatic and VDW-like H-bonds stabilize the binary clusters. This information enriches the molecular mechanism of serotonin receptors and paves a way to study the weak interactions of physiological-active molecules and also supramolecular materials.