Undergraduates improve upon published crystal structure in class assignment.

Area of Science:

• Biochemistry
• Structural Biology
• X-ray Crystallography

Background:

• Protein structure determination is crucial for understanding biological function.
• Electron density maps provide 3D structural information but require interpretation to derive amino acid sequences.
• Traditional methods often rely on prior sequence knowledge.

Purpose of the Study:

• To assess undergraduate students' ability to solve protein crystal structures without sequence information.
• To evaluate the quality of structures determined by students compared to published data.
• To explore pedagogical approaches for teaching structural biology and X-ray crystallography.

Main Methods:

• Undergraduate students were given electron density maps (1.3 Å resolution) and N-terminal residue positions.
• Students were tasked with reconstructing the protein sequence and validating structure quality.
• No prior sequence information or extensive instructor guidance was provided.

Main Results:

• Over 50% of students achieved >77% sequence identity to the original protein.
• Median structure quality ranked in the 91st percentile for comparable resolutions.
• 14% of student-derived structures showed better validation scores than the original published structure.

Conclusions:

• Undergraduate students can effectively solve crystal structures and determine protein sequences from electron density maps.
• Student-derived structures achieved high quality, sometimes surpassing original publications.
• Investigating student methodologies can inform and improve professional X-ray crystallography practices.