Chapter 7-Bioinformatics (Protein Structure and Folding) Flashcards
Describe DSSP
- performs protein sheet and helix assignments solely on the basis of backbone backbone hydrogen bonds
DSSP definition of a H bond
- bond energy is belo -0.5 kcal/mol
Condition for N-turn
5>=|i-j|>=3, H bond between residue i and j
Repeating turns form helices
Conditions for H bond to be a bridge
|i-j|>5
Repeating bridges form sheets
Describe STRIDE
- 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
What is the phi angle
Angle about the Ca-N bond
What is the psi angle
Angle about the Ca-C bond
What are the 3 states in the 3 state model?
- helix, strand, loop
Why should we predict secondary structures?
- Step towards predicting 3D structures
2. Improve other sequence and structure analysis methods e.g. sequence alignment
How to calculate basic aa propensities?
Propensity of aa to be in secondary structure=P(that particular aa in structure)/P(residues in that structure)
Problems with second generation secondary structure prediction
- Low Q3 accuracy
2. Predicted helices and strands too short
Why does normal secondary prediction not work for transmembrane proteins?
- 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
How does transmembrane protein prediction work?
- topology prediction (yields higher accuracy than prediction of sec structure of globular proteins)
- TM proteins difficult to crystallise—rather not use X ray crystallography
Describe coiled-coils prediction
- predict when 2 or more a-helices from 2 diff chains associate w each other
- based on hydrophobic interactions
Basis of signal peptide prediction
- 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
What are intrinsically disordered proteins (IDP)?
- 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
Properties of IDPs that allow their secondary structure to be predicted
- Amino acid compositional bias—disordered proteins are less likely to contain bulky hydrophobic and aromatic groups and enriched in polar and charged aa
- Low complexity—the more biased, the lower the complexity
- Sequence profile info—use aa profiles calculated from evolutionary related sequences instead of single sequence window
- Secondary structure and disorder—certain types of disordered proteins can be identifies as long regions with no predicted secondary structures
