(old) HPC: Analyze the predicted SarsCoV1-VHH.72 complex

You should have downloaded or generated AlphaFold predictions in the last step; for the SarsCoV1-VHH.72 complex can be found here (PLDDT) and here (PAE). In this exercise, we will go through the predictions and visualizations, in order to interpret them appropriately.

1. Model rankings. Determine which of the predicted structures were predicted with highest confidence. You should find a significant gap between the best model and the others. Hint: ranking_debug.json holds useful information on the predicted TM scores, which represent the global confidence of the protein complex.
2. PLDDT. Check in which regions of the complex the local confidence is high, for the top ranked model and any of the other models. The local confidence, given by a predicted LDDT score per residue, can be found in two ways.
   1. In the prefix_coverage_LDDT.png file
   2. In the PDB files, it is stored in the b-factors column. Use the YASARA / PyMol software to color residues by b-factors, which will give you a visual overview of the PLDDT.
3. PAE. The predicted aligned error is given in the prefix_PAE.png file. Inspect the file for this complex. Are there models where AlphaFold is fully confident of the prediction of the complex? Can you link the visualization to the PTM scores that you inspected in step 1.?
4. Aligning predicted structures to 6WAQ. As a final validation step for the predictions of this complex, we can compare them to the experimentally determined 6WAQ structure as found in PDB (download link). First, align the top ranked model with the second ranked model. Do you see differences? Next, align the top model to the 6WAQ structure. Do you find a good match? Try to align the second ranked model with low confidence as well. What do you see? Does this confirm what you saw in the predicted TM score ranking and the PAE plots?

Nice to know: the 6WAQ structure was co-characterized by researchers at the VIB Center for Medical Biotechnology.

Wrapp D, De Vlieger D, Corbett KS, Torres GM, Wang N, Van Breedam W, Roose K, van Schie L; VIB-CMB COVID-19 Response Team, Hoffmann M, Pöhlmann S, Graham BS, Callewaert N, Schepens B, Saelens X, McLellan JS. Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies. Cell. 2020. June 11;181(6):1436–1441. doi: 10.1016/j.cell.2020.05.047.