How to Introduce Students to Protein Structural Biology

Posted on: July 7, 2021

Why should your students study protein structural biology, and how do you introduce this topic to your course? Amit Kessel and Nir Ben-Tal, Authors of Introduction to Proteins: Structure, Function, and Motion, demonstrate how this topic is relevant to a COVID-19 world, as well as highlighting key resources for teaching and a proposed course outline.  

What is protein structural biology and why study it?

Proteins are large and complex molecules that are actively involved in the most basic and important aspects of life, as well as in disease. Accordingly, protein science is at the very center of biological research, and is applied to disciplines such as medicine, agriculture, biotechnology, and even unconventional warfare. The biological functions of proteins depend largely on their three dimensional structures and dynamics, which in turn depend on the chemical composition of proteins and on the physical forces acting on them. All these features are explored by structural biology. The insights gained from such studies allows us not only to understand better how proteins work at the molecular level, but also to apply this knowledge to more practical purposes. A powerful example for such application is given by the recent development of vaccines against coronavirus, the pathogen responsible for the COVID-19 pandemic. These vaccines deliver a coronavirus surface protein (the spike protein) into the body of the vaccinated person, directly (as protein) or indirectly (as RNA). By recognizing the protein, the person’s immune system is able to mount an efficient response against the virus. However, the spike protein is known to shift between different structures, which differ from each other in their ability to invoke effective immune response. Numerous structural studies of coronaviruses allowed scientists to find a particularly immune-relevant structure and to stabilize it by introducing mutations. This stabilized structure was then used for developing efficient vaccines.    

Challenges to teaching protein structural biology

There are two main challenges to teachers and students of protein structural biology. The first has to do with the interdisciplinary nature of the field. The students should have background in general biology, chemistry, and biochemistry, but the teacher still has to address and explain multiple chemical, biological, physical, medical, and biotechnological aspects of proteins. The second challenge is that the description of protein structure and composition requires apt graphical resources, which are often beyond the means available to teachers. Fortunately, the current wealth of resources, many of which are freely available on the web, makes these challenges surmountable. At least some of these resources are interactive, which renders the learning experience both interesting and rewarding for the students. Below, we describe of these resources.

Proposed outline for your protein structural biology course

We found that to teach protein structural biology, it is helpful to first provide the students with a general background. This includes: 

• The cellular and physiological roles of proteins, as well as their medical and industrial importance. 
• Basic chemical and physical phenomena that underlie biomolecules, mainly the types of chemical bonds found in them and the physical forces that act on them. 

After the students are familiar with this background, we move to an in-depth description of the chemical composition and structural levels of proteins, as well as experimental and computational methods for determining or predicting protein structure, respectively. These topics can be regarded as the ‘core’ of protein structural biology courses and books, but in our opinion this core is incomplete. The structure and function of proteins are significantly affected by certain physical phenomena that we believe must be discussed too. These include the thermodynamic stability of proteins, their inherent dynamics (including folding kinetics), and the physical forces that mediate ligand binding. In our courses and textbook, we also address the diverse mechanisms of enzymatic catalysis, as many proteins are enzymes.  

Resources for teaching protein structural biology

Textbooks are the most comprehensive resources for teaching and there are more than a few textbooks dedicated to protein structural biology. Many of the new textbooks offer much more than text and figures – they specify multiple links and referrals to relevant databases, web servers, and software, which provide the readers actual tools for studying proteins. In our book, we also included animations of protein dynamics and enzymatic reactions, in the form of scannable QR codes. The accompanying website also provides PyMOL files of all the protein structures shown in the book’s figures. 

In addition to textbooks, teachers and students can access many freely available educational resources, databases, web servers, tools and games, which allow interactive exploration of proteins. Here are a few examples:

• Educational resources: encyclopedias (e.g. Proteopedia), online courses (e.g. ours, and a course by Khan Academy), and tutorials (e.g. protein folding interactive tutorial by LabXchange).
• Databases: protein sequences (e.g. UniProtKB), structures (e.g. PDB, SCOP, CATH, and ECOD), domains (e.g. Pfam), functions (e.g. KEGG, BRENDA, mCSA), dynamics (e.g. molmovdb, PSCDB), ligand binding (e.g. MOAD, BioLiP), structure-function relationships (e.g. SFLD), and mutations (e.g. PMD, DRSP).
• Web servers for predicting various protein features: structure (e.g. I-TASSER, Raptor-X), function (e.g. ProFunc), evolutionary conservation (e.g. ConSurf), ligand binding (e.g. HDOCK, HADDOCK), dynamics (e.g. ANM, HingProt), and mutations effects (e.g. mCSM, PoPMuSIC).
• Visualization of protein sequence, structure, and ligand interactions: Bioedit, Jalview, PyMOL, Chimera, LigPlot, Arpeggio.
• Games and other applications: FoldIt (an interactive game that allows users to try and fold proteins into their native three-dimensional structures), Folding@Home (distributed computing of protein folding and binding, which allows users around the world to contribute to drug discovery).

Do you teach, or are considering teaching, structural biology? Request an inspection copy of Introduction to Proteins: Structure, Function, and Motion, by Amit Kessel and Nir Ben-Tal. This textbook provides a comprehensive and state-of-the-art introduction to the structure, function, and motion of proteins for students, faculty, and researchers at all levels. The accompanying website has recently been updated to include great video content too!