In silico and in vitro binding of serotonin and COMT. ( A) Structures of serotonin and S-adenosyl-L-methionine (SAM). ( B) SPR data is fitted to association and dissociation curves to determine the kinetics of serotonin binding ( k
on = 0.0012 s-1, k
off = 13.7404 M-1 s-1). (C and D) Structural modeling of serotonin within COMT active site. ( C) Surface representation of serotonin binding to a pocket within COMT. Serotonin structure is shown in cyan; SAM structure is shown in green. The overlapped structures indicate that the amine sidechain of serotonin prevents SAM from actually binding to COMT. On the COMT surface, blue represents positively-charged, red represents negatively-charged, and white represents neutrally-charged regions. ( D) Interactions of serotonin with residues inside COMT active site. COMT structure and residues are shown in green; serotonin is shown in blue. Hydrogen-bonding interactions are highlighted with yellow-dashed lines.