Lecture 9 DA Flashcards Preview

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Flashcards in Lecture 9 DA Deck (45):
1

What is a limitation of x-ray crystallography?

It is just a snapshot of the crystal, at that moment in time. Crystals move and vibrate etc.

2

Is the structure of a protein sufficient to determine its function?

Yes, but for some proteins only, like structural proteins.

3

How are some amino acids important in correct biological activity in some proteins?

The active site of proteins with biological activity (ie enzymes) is formed by crucial amino acids.

4

Do secondary structures of proteins form as the mRNA is translated, or once completely translated?

As it is being translated.

5

What typically mediates complete folding of proteins?

Chaperones, but not always.

6

How do chaperones bind to their target?

Via hydrophobic interactions.

7

Where would evolution of amino acids be faster/slower, in the core, or on the surface?

Evolution is slower in core amino acids, whilst faster with surface ones.

8

Are surface amino acids hydrophobic or -philic? What about core amino acids?

Core - hydrophobic
Surface - typically phydrophilic, but can be hydrophobic - ie clefts/active sites.

9

What kind of architecture do proteins have?

Modular architecture.

10

What kinds of proteins are the most difficult to crystallise and model? How are they typically crystallised?

Membrane spanning proteins. Easier to co-crystallise them with another protein that masks their hydrophobicity, and can be adjusted via algorithms for a pure dataset.

11

What percentage of proteins are membrane spanning?

20%

12

What percentage of drugs target a protein as its causative action?

50%

13

The conformation of the backbone of amino acids is defined by what?

Phi and psi angles.

14

Which amino acid has no angles of freedom? What about the most?

Proline - none
Glycine - most

15

True or false
Most angles of phi and psi are allowed.

False

16

What secondary structure can be found in each quadrant of the Ramachandran plot?

Top left - b-sheets
Top right - left-handed a-helix
Bottom left - right handed a-helix
Bottom right - NA

17

Which secondary structure is most common?

Right handed a-helix

18

What entirely dictates protein folding?

Primary sequence

19

What is the Darwinian principle of protein evolution?

Proteins evolved from a common ancestor have similar folding.

20

What does the algorithm based on Darwinian principles of protein evolution do?

Detects sequence similarity.

21

What is the Boltzmann principle of protein folding?

Proteins search for conformational space, minimising their free energy.

22

What does the algorithm based on Boltzmann principle of protein folding do?

simulates folding process.

23

What is the function of ubiquitin?

Tags misfolded/unfolded proteins for digestion via a proteosome.

24

When proteins are digested by a proteosome for being un/misfolded, what happens to them? How does this affect infection?

They go to the ER, and are put on MHC markers for display on the cell surface.
When infected, pathogen proteins will be displayed instead, allowing the immune system to be alerted.

25

What is the primary repository for protein structures? What else does it contain? What tool can be used to search it?

Protein databank PDB.
Also contains DNA/RNA structures.
Searched with BLAST.

26

Are new folds currently being found?

No

27

Is there a finite number of folds, or is it infinite? Why?

Predicted to be finite, as there are a finite number of superfamilies.

28

What does it mean if proteins have the same fold? What else points to this? Do they have sequence similarity?

Major structural similarity between the two.
Secondary structure must be in the same arrangement, with same overall topology.
Generally no sequence similarity.

29

What does it mean if two proteins are in the same superfamily?

Probably common evolutionary origin, low sequence identity.

30

What does it mean if two proteins are in the same family?

Clear evolutionary relationship, with moderate to high sequence similarity - >30% pairwise identity.

31

Name and describe two protein structure comparison methods.

Protein sequence matching - applies dynamic programming to the problem of string matching, and uses a scoring scheme.
3D protein structure matching - uses algorithms similar to dynamic programming that finds optimal match between two shapes.

32

How does the algorithm behind 3D protein structure matching work?

Looks at dihedral angles, phi and psi, and draws a distance matrix.

33

How do some tools like DALI search for matching structures among proteins?

Splits searches into hexapeptides, and finds all matching hexapeptides.
Concatenates matching hexapeptides using simulated annealing.

34

Name 4 modelling techniques.

Predicting secondary structures.
Homology modelling
Fold recognition
De novo prediction

35

How can homologues sometimes be recognised when predicting secondary structures?

By similar patterns of secondary structures.

36

Which modelling technique is generally the most accurate? What does it require?

Homology modelling. Requires a homolog with a known structure.

37

What does de novo prediction use as the basis for its prediction?

The primary sequence is used.

38

What are the steps of homology modelling (4)?

-Homologs of known structures are identified
-High quality alignment of the sequence in question with the protein of known structure.
-Run modelling algorithm. Different residues between the sequences are changed, and the consequence to overall structure evaluated.
-Model is evaluated for unacceptable stearic clashes (Ramachandran plot)

39

What can be used to identify distantly related homologs?

Psi-BLAST

40

How does fold recognition work (threading)?

Looks for a compatible fold for a given sequence.

41

What is threading/fold recognition used in (3+)?

Profile matching, secondary structure prediction, alignments, etc

42

When is the ab initio method used? What does it attempt to predict, and from what?

When the sequence cannot be assigned to a known fold.
It attempts to predict the structure from the primary sequence.

43

How important is the ab initio method for fold predictions?

It is less important in fold predicting, but still important for refinement of strucure.

44

Is it possible to obtain a high quality structure prediction from the primary sequence alone (with no reference protein/sequence)?

No.

45

What is the thermodynamic hypothesis?

Protein is looking for the free energy minimum state.