title: Undergraduates improve upon published crystal structure in class assignment.
abstract: Recently, 57 undergraduate students at the University of Michigan were assigned the task of solving a crystal structure, given only the electron density map of a 1.3 Å crystal structure from the electron density server, and the position of the N-terminal amino acid. To test their knowledge of amino acid chemistry, the students were not given the protein sequence. With minimal direction from the instructor on how the students should complete the assignment, the students fared remarkably well in this task, with over half the class able to reconstruct the original sequence with over 77% sequence identity, and with structures whose median ranked in the 91(st) percentile of all structures of comparable resolution in terms of structure quality. Fourteen percent of the students' structures produced Molprobity steric clash validation scores even better than that of the original structure, suggesting that multiple students achieved an improvement in the overall structure quality compared to the published structure. Students were able to delineate limiting case chemical environments, such as charged interactions or complete solvent exposure, but were less able to distinguish finer details of hydrogen bonding or hydrophobicity. Our results prompt several questions: why were students able to perform so well in their structural validation scores? How were some students able to outperform the 88% sequence identity mark that would constitute a perfect score, given the level of degenerate density or surface residues with poor density? And how can the methodology used by the best students inform the practices of professional X-ray crystallographers?
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, 48109.
authors.forename: Scott
authors.initials: S
authors.lastname: Horowitz
authors.forename: Philipp
authors.initials: P
authors.lastname: Koldewey
authors.forename: James C
authors.initials: JC
authors.lastname: Bardwell
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D003460:Crystallization; D018360:Crystallography, X-Ray; D003479:Curriculum; D006801:Humans; D009042:Motivation; D018794:Problem-Based Learning; D011506:Proteins / Q000737:chemistry; D015203:Reproducibility of Results; D013334:Students; D011795:Surveys and Questionnaires; D013663:Teaching / Q000379:methods*; D014495:Universities
chemical_list: D000596:Amino Acids; D011506:Proteins
keywords: active learning; assessment and the design of probes for student understanding and learning; biophysical methods; computational biology; laboratory exercises; learning and curriculum design; problem-based learning; protein structure function and folding