The Future of Structural Biology
AlphaFold
Breaking Down Discussion Sections
Foundations of Structural Biology
100
Name one of the 5 Frontiers of Structural Biology discussed in class. 

What is...

Sample preparation
In situ Cellular
Structural Dynamics
Translation Biology
AI

100

What structural database was used to train AlphaFold? (full name; no acronyms) 

What is Protein Data Bank 

100

The following statement from today's assigned reading can be find in which section of the discussion: 

"AlphaFold2 can predict the structures of most globular proteins to near atomic-level accuracy. However, approximately 30% of the human proteome is intrinsically disordered, with over 60% of all human proteins containing at least one IDR longer than 30 residues in length." 

(Options: Gap in knowledge, Summary of findings, Interpretations of results, Implications, Limitations, Future Direction)

What is Gap in Knowledge

100

What does NMR stand for?

What is Nuclear Magnetic Resonance

200

What is the protein folding problem?

What is predicting how a protein's amino acid sequence dictates its unique three-dimensional structure 

200

What information does AlphaFold need to predict a protein structure?

What is the amino acid sequence 

200

The following statement from today's assigned reading can be find in which section of the discussion: 

"The complementary nature of AlphaFold2 structural predictions and atomic-level insight from NMR spectroscopy will be pivotal for future developments related to IDR conformational ensembles."

(Options: Gap in knowledge, Summary of findings, Interpretations of results, Implications, Limitations, Future Direction)

What is Future Directions

200

Why is it challenging to study large membrane proteins using X-Ray Crystallography? 

What is Ease of Crystallization

300

What software can be used to predict the structure of protein complexes and protein-protein interface structures?

What is AlphaFold-Multimer 

300

If a section of a predicted protein structure is colored YELLOW, what does that mean?

What is low confidence score

300

The following statement from today's assigned reading can be find in which section of the discussion: 

"Our finding that AlphaFold2 has learned to identify conditionally folded IDRs will enable insights into the sequences, evolution, and structural bioinformatics of these regions."

(Options: Gap in knowledge, Summary of findings, Interpretations of results, Implications, Limitations, Future Direction)

What is Implications 

300

Which structural method would work best in study a small, highly dynamic globular protein? 

What is NMR

400

Why are IDRs and IDPs an ongoing challenge for structural biologist?

What is their lack of stable structures and rapid interconversion between different conformations make identifying important functional states challenging. 

400

In what FIELD and YEAR did the creators of AlphaFold win the Nobel Prize?

What is Chemistry and 2024

400

The following statement from today's assigned reading can be find in which section of the discussion: 

"Collectively, these results lead to the hypothesis that if only 15 to 25% of human IDRs are conditionally folded, then the majority of IDRs in the human proteome, and those of other eukaryotes, would function in the absence of stable structure."

(Options: Gap in knowledge, Summary of findings, Interpretations of results, Implications, Limitations, Future Direction)

What is Interpretation of results 

400

What is the name/term of the sample preparation technique used in cryo-EM?

What is vitrification

500

How might AI be used to revolutionize drug discovery?

What is AI models can be used to predict how and where molecules bind to a therapeutic protein target. 

500

Name the two confidence metrics used to score an AlphaFold predicted protein structure (will accept acronyms) 

What is predicted local distance difference test (pLDDT) and Predicted Aligned Error (PAE) 

500

The following statement from today's assigned reading can be find in which 2 sections of the discussion: 

"At present, we do not know the rate with which AlphaFold2 incorrectly predicts conditionally folded IDRs..."

(Options: Gap in knowledge, Summary of findings, Interpretations of results, Implications, Limitations, Future Direction)

What is Gap in Knowledge and Limitation 

500

You are studying two very similar proteins, both of which have fairly stable structures (not flexible or dynamic). 

If using cryo-EM, which protein would have a higher resolution given the number of protein particles picked during data analysis. 

What is the protein structure with more protein particles will likely have a higher resolution