Chapter 7-Bioinformatics (Protein Structure and Folding)

Question 1

Describe DSSP

Answer 1

• performs protein sheet and helix assignments solely on the basis of backbone backbone hydrogen bonds

Question 2

DSSP definition of a H bond

Answer 2

• bond energy is belo -0.5 kcal/mol

Question 3

Condition for N-turn

Answer 3

5>=|i-j|>=3, H bond between residue i and j

Repeating turns form helices

Question 4

Conditions for H bond to be a bridge

Answer 4

|i-j|>5

Repeating bridges form sheets

Question 5

Describe STRIDE

Answer 5

• uses empirically derived H bond energy and phi-psi torsion angle criteria to assign secondary structure
• torsion angles given alpha helix and beta sheet propensities according to how close they are to their regions in ramachandran plots

Question 6

What is the phi angle

Answer 6

Angle about the Ca-N bond

Question 7

What is the psi angle

Answer 7

Angle about the Ca-C bond

Question 8

What are the 3 states in the 3 state model?

Answer 8

• helix, strand, loop

Question 9

Why should we predict secondary structures?

Answer 9

1. Step towards predicting 3D structures

2. Improve other sequence and structure analysis methods e.g. sequence alignment

Question 10

How to calculate basic aa propensities?

Answer 10

Propensity of aa to be in secondary structure=P(that particular aa in structure)/P(residues in that structure)

Question 11

Problems with second generation secondary structure prediction

Answer 11

1. Low Q3 accuracy

2. Predicted helices and strands too short

Question 12

Why does normal secondary prediction not work for transmembrane proteins?

Answer 12

• different sec structure propensities for amino acids in water and in membranes
• normal prediction methods trained in knowledge derived from databases and membrane proteins are underrepresented there

Question 13

How does transmembrane protein prediction work?

Answer 13

• topology prediction (yields higher accuracy than prediction of sec structure of globular proteins)
• TM proteins difficult to crystallise—rather not use X ray crystallography

Question 14

Describe coiled-coils prediction

Answer 14

• predict when 2 or more a-helices from 2 diff chains associate w each other
• based on hydrophobic interactions

Question 15

Basis of signal peptide prediction

Answer 15

• positively charged n region, followed by hydrophobic h region and a neutral but polar c region
• (-3,-1) rule states that residues at positions -3 and -1 relative to cleavage site must be small and neutral for cleavage to occur correctly

Question 16

What are intrinsically disordered proteins (IDP)?

Answer 16

• large number of naturally occurring proteins that do not require a well-folded structure to fulfil their biological role
• exist as ensembles of rapidly interconverting conformations
• unexpectedly high frequency in proteomes
• participate in impt regulatory functions in the cell including transcription, translation and cell signalling

Question 17

Properties of IDPs that allow their secondary structure to be predicted

Answer 17

1. Amino acid compositional bias—disordered proteins are less likely to contain bulky hydrophobic and aromatic groups and enriched in polar and charged aa
2. Low complexity—the more biased, the lower the complexity
3. Sequence profile info—use aa profiles calculated from evolutionary related sequences instead of single sequence window
4. Secondary structure and disorder—certain types of disordered proteins can be identifies as long regions with no predicted secondary structures