Structural Chemistry and Biochemistry
Taught by: Miriam Rossi
What is your "Structural Chemistry and Biochemistry" course about? Tell us about its origin, goals and objectives.?
Today, interdisciplinary research and areas of study are the norm in the sciences. The borderlines of research in chemistry, biology, physics, geology are vanishing and increasingly, molecular interactions and chemical transformations are found to be at the heart of biology, biochemical and biomedical phenomena as well as understanding the behavior of new materials, material sciences and geological sciences. For example, many diseases and their treatment are molecular in nature and medicinal chemistry and pharmaceutical companies have large components dedicated to drug design research that has structural information as its basis.
This course was developed to make students aware that the same fundamental principles that govern the molecular architecture for metals and small salt compounds also explain the structures of macromolecules and molecular assemblies such as viruses. General texts in chemistry, biology, geology, biochemistry and solid-state physics are full of molecular structure representations obtained from the three-dimensional atomic coordinates determined by X-ray diffraction. Unfortunately, there is difficulty in interpreting these spatial arrangements, especially as the structures of increasingly larger molecules become available. This problem is not new. In 1925, Sir William Bragg (awarded the Nobel Prize in Physics 1915 "for the analysis of crystal structure by means of X-rays") wrote in the Preface to his book, Concerning the Nature of Things: "If one can turn over a model in one's hand, an idea can be seized in a mere fraction of the time that is required to read about it, and a still smaller fraction of the time that is required to prepare the description."
The goals of this course involve familiarizing students with basic concepts of molecular structure and geometry, chemical bonding and intermolecular interactions; to introduce students to X-ray crystallographic methods for determining molecular structure; how to read a crystal structure paper; to study the structures of molecules of chemical and biological interest; interpreting the complex images that accompany structural papers. The overall aim is to see how the molecular structure is one of the determinant features responsible for chemical and/or biological activity. It is an advanced level course open to chemistry and biochemistry majors or students declaring a chemistry or biochemistry correlate sequence.
I am able to attain these goals by using different computer programs and databases that can be accessed in a computer classroom. Cristian Opazo, Academic Computing Consultant who is a science computation specialist maintains this computer classroom; his presence has ensured the successful outcome of this course.
What were the technologies used and how did they change or enhance your course?
I use two main computer tools: the Protein Data Bank (PDB), a large repository for the processing and distribution of 3-D biological macromolecular structure data and, the Cambridge Crystallographic Structural Database (CCSD), which is a database of bibliographic, chemical and crystallographic information for organic molecules and organometallic compounds. The CCSD is not freely available, but fortunately the college has a campus-wide license for it, so every student can access it either locally on lab computers or via Citrix from anywhere on campus. The Protein Data Bank is freely and widely available on the web at http://www.rcsb.org/pdb/
The addition of these tools has made a huge difference in teaching this course. For example, the various visualization capabilities available in the two databases make the content easier to teach, since many structural features become self-evident when they are viewed. The ability to manipulate, rotate and edit structures allows instructors to convey these structural ãrulesä that are not easy to visualize or understand otherwise. This is essential for understanding three-dimensional structural data, particularly macromolecular data; therefore, the two structural databases are an indispensable resource to achieve this objective.
The Student Response
How have your students responded to your use of technology?
Students are very receptive to acquire information through interactive and visual experience. I hear students praise the software all the time; they like being able to see and manipulate molecules; it is intuitive, easy and fun. Frequently, in courses where the concepts of molecular shape and chemical properties derived from molecular shapes are introduced, for example, organic chemistry, students use model kits as a teaching aid. While this is a useful exercise, being able to rotate the structure on the screen and see how a molecule interacts with others is especially valuable. The use of these structural databases reinforces material that they learn about in their textbooks. It becomes clear that the connections between atoms to make molecules and how molecules are grouped together to make molecular assemblies all have similar foundations. Geometrical details can be calculated easily and displayed. It has made describing molecular features much easier and since students can access the PDB anytime using an Internet connection makes it very flexible for students to use- they can access information for problem sets at their convenience.
The use of interactive computer graphics software is especially indispensable when teaching macromolecular structure. The level of complexity in macromolecular structure is astounding. Proteins can have diverse shapes or motifs that make up their final 3-D structure. It is here that the PDB becomes such useful teaching tool: it permits students to look at the complex protein or other large macromolecular assembly using options that permit a different perspective by zooming in to a particular site, rotating the structure. It becomes possible to view the same structural motif in many proteins, allowing for interesting discussion to take place in the classroom: the PDB reinforces material that they learn about in their textbooks. Geometrical details can be calculated easily and displayed. The Molecule of the Month feature is outstanding and almost forms the basis for the macromolecular part of this course; it features an in-depth look at a collection of well-studied molecules. It provides a well-written introduction to a molecule, its biological importance, how the structural features are utilized by the molecule to attain its function, and highlights the use of common structural motifs by related compounds. My students use this feature as a starting point in many of their in-depth analyses that are required for homework assignments. What I have found is that because the PDB is easy to use, students literally can spend hours manipulating these complex structures. And, every instructor knows that the more time a student spends on trying to understand course material, the more attracted they become to the subject.
Every year, I try to shape the course contents taking into account the particular interests of my students. They really enjoy being able to use these databases to find and visualize well-known structures they learn about in other contexts; for example, they can see how toxins such as cholera or anthrax toxins behave at an atomic level, as well as the common cold and influenza viruses. Some of the topics we discuss are how DNA modifies its shape as it interacts with a variety of proteins; the mathematical description of the morphology of virus particles, etc. Since students pick a topic for an end-of-the-year presentation, sometimes I get to see really interesting things happening in the classroom. I remember that a student who was an Art History major gave a presentation about the composition of different colors of paint throughout history, from the point of view of their structural and molecular constituents.
What were the challenges you faced when teaching this course?
Even though these computer programs are very well built, and easy to use, there is always a learning curve that students must go through. Most of them are very quick learners, but with a few one has to be more patient and guide them through the first couple of sessions. For example, seeing complex protein structural patterns such as the Greek key motif need to be explained one-on-one. A good idea would be having an experienced student assistant helping students during lecture time.top
What new directions would you like to explore technology in your teaching?
I would like to explore the possibility to use software that, in addition to showing still structures, also displays molecular motion and the dynamics of molecular binding. This area, called Molecular Dynamics, is important research topic these days and I am interested to cover it more in detail in the future.top