Protein secondary structure prediction methods

TDVEAAVNSLVNLYLQASYLS

“From sequence to structure”

• What are they?– Sequence-based tools for protein

structure prediction.

• What do they do?

1.they Search for similar protein sequences in a database.

2.Based on the similarity to these sequences they predict aspects of protein structure and function

What kind of prediction can we perform?

– Secondary Structure: Helix, Strands, Loops (PHDsec,PSIPRED).

– Predicts transmembrane helices (PHDhtm,MEMSAT,TMHMM).

– Fold structure (genTHREADER). – Solvent accessibility: important for the prediction of ligand binding sites (PHDacc).

– Other features: Coiled Coils, Globular regions, Disulfide Bonds and more…

Secondary Structure prediction:

Query

SwissProt

BLASTp

QuerySubjectSubjectSubjectSubject

psiBLAST,MaxHom MSA

Machine LearningApproach

HHHLLLHHHEEE

Known structures

PROFsec and PSIpred

Two secondary structure prediction tools:

• PROFsec– Based on sequence family alignments (MAXHOM)

• PSIpred– Based on PSI-BLAST profiles

http://www.predictprotein.org/

Input

Output

PSIpred

Input sequence

Type of Analysis(PSIPRED,MEMSAT,

genTHREAD)

http://bioinf.cs.ucl.ac.uk/software_downloads/

http://bioinf.cs.ucl.ac.uk/web_servers/

PSIPRED secondary structure prediction

PROFsec PSIpred

?

?

TMHMM – transmembrane domain prediction

http://www.cbs.dtu.dk/services/TMHMM/

Predict Start End

Sequence and SecondaryStructure

information

Sequence DetailsTurn Helix

Excersize The sequence below belongs to the Prion that causes the “mad cow” disease. This protein becomes toxic

when it gets into the brain and misfolds causing native cellular prions to deform and aggregate. In structural terms, the prion toxicity in leaded by a folding change into an instable structure.

 

>PRION_1ag2

GLGGYMLGSAMSRPMIHFGNDWEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCVTQYQKESQAYY

1. Use Predict Protein (PROFsec) to predict its secondary structures.

2. What is the secondary structure in the real solved structure based on the PDB?

3. Given the prediction results and the secondary structure of the real solved structure can you suggest the region which could be responsible for the structural instability?  

1. Predict Protein (PROFsec)

2. PDB (DSSP)

3. Answer : alpha helix PDB (DSSP)turn into B-sheet Predict Protein (ROFsec),

prediction in this area are not consistent.