A. Review the answers to the pre-activity exercises in your group to make sure that everyone is on the same page. This should take no more than five (5) minutes.
B. Examine the structure of the neurotransmitter serotonin shown below.
Determine which of the forces or bonds listed below can be used to provide the optimal environment for binding of the serotonin molecule to another molecule (e.g., receptor, transporter, etc.). Decide “yes” or “no” and then give a brief one-sentence explanation.
1. London dispersion forces (a.k.a. van der Waals)________________________________
C. (Time 0:15 min) How many hydrogen atoms in the serotonin molecule can be “donated” to make hydrogen bonds? Label those sites on the molecule shown below.
How many hydrogen bonds can the serotonin molecule “accept” from other molecules? Label those sites on the molecule shown below.
D. Examine the figure shown below. Determine which intermolecular force would provide the best or strongest interaction with the serotonin molecule at the specific points labeled A, B, and C. Once you decide on the interaction present at a given position (A, B, C), you should assume that the interaction remains at that position for the rest of the questions that follow. Briefly explain your choices in the spaces below (see next page).
Position A (interaction with ONLY the benzene ring in serotonin): ___________________________________________________________
Position B (interaction with the hydrogen atom of the N-H bond): ___________________________________________________________
E. (Time 0:30 min) Some bonds in the serotonin molecule are free to rotate. Would the conformer of serotonin shown below bind more tightly, less tightly or about the same to the binding site that you defined in Part D? Briefly explain your reasoning.
F. An increase in pH would change the ionic charges on the serotonin molecule. Examine the form of the serotonin molecule shown below. Would this charged form bind more tightly, less tightly or about the same to the binding site that you defined in Part D? Briefly explain your reasoning.
G. Assume that the serotonin molecule entered the binding site that you defined in Part D in the “flipped” orientation shown below. Briefly explain whether the serotonin molecule will bind about as tightly, much less tightly or much more tightly in the flipped orientation.
H. (Time 0:40 min) Other metabolites found in the extracellular fluid might also wander into the serotonin binding space. Again, assume that the interactions present at sites A, B and C remain unchanged from those that you defined in Part D. Examine the possibilities shown below and assess the ability of each metabolite to bind as tightly as serotonin.
The molecule dopamine (shown below) is also a neurotransmitter with a structure similar to serotonin. Briefly explain whether dopamine binds about as tightly, much less tightly or much more tightly than serotonin to the receptor site.
The glucose molecule (shown below) is a common metabolite found in most cells. Briefly explain whether glucose binds about as tightly, much less tightly or much more tightly than serotonin to the receptor site.
Tryptophan (shown below) is an amino acid that is also a precursor in the biosynthesis of serotonin.
Briefly explain whether tryptophan binds about as tightly, much less tightly or much more tightly than serotonin to the receptor site.
How might evolutionary pressures have driven changes to prevent the binding of tryptophan to the serotonin binding pocket without disrupting the interactions responsible for serotonin binding?