Visual assessment of AlphaFold2-predicted possible transcytosis protein structures

Transcytosis proteins are important for drug delivery owing to their selective transfer of substances through biological barriers [1], and their structures have been extensively studied [2]. Using AlphaFold2 (AF2) [3] it is now possible to predict the 3D structure of proteins; however, evaluation of the predicted structures is still required before further scrutiny of these proteins. For this study, we extracted ~100 protein structures with relevant sequence motifs identified in the literature, from the https://alphafold.ebi.ac.uk/ database, and we will use these structures for further analysis.
To perform the analyzes, the structures will first be visualized using VMD [4] and/or ChrimeraX [5], and secondary structural elements (such as helices, strands, and coils) will be examined. Structures will be colored based on their predictive value (lddt) and checked for visual anomalies. Experimental structures of these proteins will be downloaded from the PDB database [6] and superimposed on the predicted structures to understand the differences. Finally, amino acids belonging to sequence motifs will be visualized for predicted and/or experimental structures, and again their lddt scores will be examined. Based on the findings, more in-depth discussions using various analyzes such as hydrogen bonds and surface area calculations may be required.
By the end of this project, students will learn about protein prediction, visualization of 3D structures, and evaluation of predicted protein structures. The relationship between protein structure and biological function will be discussed.
 
[1]        V. M. Pulgar, “Transcytosis to Cross the Blood Brain Barrier, New Advancements and Challenges,” Front. Neurosci., vol. 12, p. 1019, Jan. 2019, doi: 10.3389/fnins.2018.01019.
[2]        D. D. Sahtoe et al., “Transferrin receptor targeting by de novo sheet extension,” Proc. Natl. Acad. Sci. U.S.A., vol. 118, no. 17, p. e2021569118, Apr. 2021, doi: 10.1073/pnas.2021569118.
[3]        J. Jumper et al., “Highly accurate protein structure prediction with AlphaFold,” Nature, vol. 596, no. 7873, pp. 583–589, 2021, doi: 10.1038/s41586-021-03819-2.
[4]        W. Humphrey, A. Dalke, and K. Schulten, “VMD: Visual molecular dynamics,” Journal of Molecular Graphics, vol. 14, no. 1, pp. 33–38, Feb. 1996, doi: 10.1016/0263-7855(96)00018-5.
[5]        E. F. Pettersen et al., “UCSF ChimeraX : Structure visualization for researchers, educators, and developers,” Protein Science, vol. 30, no. 1, pp. 70–82, Jan. 2021, doi: 10.1002/pro.3943.
[6]        G. Gilliland et al., “The Protein Data Bank,” Nucleic Acids Research, vol. 28, no. 1, pp. 235–242, Jan. 2000, doi: 10.1093/nar/28.1.235.