Serotonin in the pocket:

noncovalent interactions and neurotransmitter binding

I.The Importance of Selective Binding

The recognition by a nerve cell that the neurotransmitter serotonin has appeared may, or may not, trigger a response by the nerve cell. Recognition of the serotonin molecule occurs when nerve cells have receptor molecules that selectively bind serotonin. By exploring how a serotonin receptor selectively recognizes serotonin, one will learn the general principles of selective binding that are found in many biochemical processes including enzyme-substrate binding, antigen-antibody binding, hormone-receptor binding and many, many more.

The introduction to selective binding will begin with a review of the different forces that may be used when molecules bind or stick together. It is important to note that a specific binding interaction may use one or more of the forces listed below. There is no requirement that every force be used in every binding interaction. For example, ionic bonds are not required to explain the relatively high boiling point of water. Likewise, some forces may used more than once with a given molecule. Using water again, each water molecule can participate in four different hydrogen bonds with neighboring water molecules.

After reviewing the forces in the pre-activity, the in-class exercise will examine the possible forces that might be used to “stick” a serotonin molecule to a nerve cell receptor. Later in the semester, the course will delve into how a protein molecule (e.g., a nerve cell receptor, an enzyme, an antibody, etc.) can create a specific binding site or binding pocket.

II. Binding Forces

A. Write a brief, one or two sentence, description of each binding force listed below.

1. London dispersion forces (a.k.a. van der Waals)______

______

______

______

2. Dipole-dipole forces ______

______

______

______

3. Hydrogen bonding ______

______

______

______

4. Ionic interactions ______

______

______

______

5. Hydrophobic interactions (note: Hydrophobic interactions appear where you might expect van der Waals interactions from organic chemistry. But, they are stronger and use a different mechanism.)

______

______

______

6. Covalent bonds ______

______

______

B. Characteristics of Chemical Forces Responsible for Binding Interactions.

(Note: some of the values needed are from Table 1.3 in Garrett & Grisham/4e and the rest are available from other sources…)

Binding Force / Strength (kJ/mol) / Distance (nm) / Reference
Van der Waal’s (London)
Hydrogen bonds
Ionic interactions
Hydrophobic effect / Not applicable
Covalent bonds
(e.g., C-C, C-H)