Teaching Noncovalent Interactions in the Biochemistry Curriculum through Molecular Visualization: The Search for pi Interactions

Teaching students how proteins adopt a stable three-dimensional structure is a major goal in the biochemistry curriculum. Inherent in this task is the introduction of the structure of the amino acids and the various types of noncovalent interactions. When these two topics are taught together, the students gain a better appreciation for the importance of noncovalent interactions in stabilizing the structure of proteins and protein complexes. Biochemistry textbooks have not recognized the ability of aromatic amino acids to participate in π interactions with other amino acids and the role of these interactions in protein stability. To introduce these ideas, RasMol, a molecular visualization program, was used by students to search for specific examples of noncovalent interactions in a variety of protein structures. The students found examples of the traditional weak interactions as well as examples of stabilizing interactions involving aromatic amino acids. These interactions are described in this report and can be viewed at an accompanying Web site. This work clearly demonstrates that π-type interactions help stabilize the structure and complexes of many proteins and that such interactions should be integrated into the biochemistry curriculum.