- What two microscopic features did Alois Alzheimer find in Auguste Deter's brain after her death?
Protein Folding
How proteins acquire their functional shapes.
- How did solving haemoglobin and myoglobin's structures give rise to structural biology as a discipline?
- Why does a protein's three-dimensional fold determine its biological function?
- What did Anfinsen's ribonuclease A experiments show about how a protein knows what shape to fold into?
- What is the thermodynamic hypothesis of protein folding, and why did it matter that a denatured protein could refold on its own?
- How does Anfinsen's thermodynamic hypothesis connect to modern tools like AlphaFold?
- Why was kuru, the disease Gajdusek studied among the Fore people, transmitted through the ritual consumption of the dead?
- What made kuru's infectious agent seem impossible given that it had no detectable DNA or RNA?
- How did Gajdusek's work on kuru's slow infectious agent later connect to the discovery of prions and BSE?
- Why did diseases like scrapie and kuru puzzle virologists who could find no nucleic acid transmitting them?
- What is a prion, and how does a misfolded protein induce neighbouring proteins to misfold as well?
- Why did Stanley Prusiner's proposal violate a principle molecular biologists considered settled about how biological information flows?
- How did the prion hypothesis eventually explain mad cow disease and its human variant?
- How does knowing where hydrogen atoms sit help explain how proteins fold?
- How can a misfolded protein spread disease without any DNA or RNA involved?
- Why did Prusiner's prion hypothesis contradict the central dogma of molecular biology so directly?
- What diseases in sheep and humans led Prusiner to his theory of infectious proteins?
- How did the prion mechanism later connect to research on Alzheimer's and Parkinson's disease?
- What are molecular chaperones, and how do they help proteins fold correctly?
- How does the GroEL/GroES complex protect a newly made protein chain from misfolding?
- Why is protein misfolding connected to diseases like Alzheimer's and Parkinson's?
- What impact did multiscale simulation methods have on modern drug discovery?
- What is the unfolded protein response and how does it let a cell detect misfolded proteins?
- Why do neurodegenerative diseases like Parkinson's and ALS involve the same pathway Mori and Walter mapped?
- Why is reversing protein denaturation relevant to diseases like Alzheimer's?
- What did Christian Anfinsen's Nobel-winning work establish about how a protein's shape relates to its amino acid sequence?
- How did the CASP competition measure progress on the protein-folding problem for over two decades?
- What accuracy did DeepMind's AlphaFold2 achieve at CASP14, and how did it compare to X-ray crystallography?
- Why did a machine-learning approach succeed where decades of molecular dynamics simulation had struggled?
- What is the protein-folding problem, and why had it resisted solution for fifty years?
- How accurate was AlphaFold 2 compared to experimental structures at the CASP competition?
- How did the AlphaFold protein structure database change the work of structural biologists who couldn't crystallise their proteins?
- What did Anfinsen's 1962 work show about the relationship between a protein's amino acid sequence and its three-dimensional shape?
- How does AlphaFold2 predict a protein's structure directly from its sequence, and how accurate is it compared to experimental methods?
- How did solving the protein-folding problem change the questions structural biologists ask?