Crystallography

In the context of structural biology: The study of macromolecular structure and function to inform and inspire development of treatments against diseases

Macromolecular crystallography is the study of macromolecular structure and function and is a four-step process requiring protein/nucleic acid expression and purification, crystal-growth and optimization, crystal harvesting and diffraction data collection, and model building and refinement.

The four-step process of crystallography: (1) Protein expression, (2) crystal-growth and optimization, (3) diffraction data collection, and (4) model building and refinement. The structure can provide insight on active sites, catalytic residues, and inform structure-based design of therapeutic treatments.

Determining the structures of nucleic acid their protein complexes allows us to understand their active sites and catalytic residues, which helps us understand the protein/nucleic acid activity.

Insight about the protein/nucleic acid function and their molecular basis is important for designing and discovering new structure-based therapeutics to target and treat diseases such as cancer.

Here is an example where a structural study was performed and an inhibitor was designed against SARS-CoV-2 3CLpro, a viral protein crucial for virus proliferation, with potent 3CLpro inhibition (single digit nanomolar IC50 values against 3CLpro in cell-free assays and with a 500-fold selectivity index against other proteases) and anti-coronavirus activity in animal models: Fig. 1: EDP-235 inhibits SARS-CoV-2 3CLpro and binds reversibly to 3CLpro’s active site. | Nature Communications

Structure-based therapeutic drug discovery, such as the designing of small molecule inhibitors, PROTACS, or polypeptide inhibitors to target protein drivers in certain diseases, is possible through structure determination and crystallography

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Learning how to set up protein crystallization experiments, grow protein crystals, and solve structures from electron density maps with research-grade equipment and software give students a taste of what real crystallography research is like without the traditional time, faculty mentor, research space, and research materials barriers to undergraduate or high school research.

Jan. 2024 Crystallography Workshop, students learning how to micropipette for setting up crystal trays.

Not only are the micropipette experiments for crystal tray setting relatively easy to learn, but they also provide students with basic biology wet-lab training that can be useful in their instructional biology labs or undergraduate biology research.

Learning about the process of crystallography and its significance for therapeutic drug discovery can help students understand the training and theory that they are using and provide them with related basic research skills with which they can use for their own research endeavors.

Practicing their wet-lab, computational, and research presentation skills helps them become more confident in the research space.

Fall 2024 STARS Atlanta branch club meeting, Addie Kindler presenting about the history of Oak Ridge National Laboratory (ORNL) in preparation for the ORNL trip

Attending and presenting at annual American Crystallographic Association (ACA) conferences provide students the chance to see what the realm of crystallography is like, as they interact with exhibiting companies and interact with fellow attendees, practicing and improving their communication and presentation skills, while giving their talks and attending discussions.

2023 American Crystallographic Association (ACA) conference, Susanna Huang presenting about the Se-modified nucleic acid crystallization technique

Crystallography is important for determining structures and designing therapeutics. Crystallography additionally is unique that its experimental component comes in the form of beautiful crystals. We use the beauty and importance of crystallography through our crystallography workshops, club meetings, and conference attending to captivate and inspire students in therapeutic drug discovery, foster research-focused student communities, and create student-faculty networks for research and STARS collaborations.

We strive to expose vanguard macromolecular crystallography to students and members and to nurture their curiosity and passion in crystallization, structure determination, macromolecular modeling, bioinformatics, small molecule design, bioactivity study, and drug discovery.