Session ii g2 overview protein modeling mmc

Protein Homology Modeling

Introduction• What is protein?

- providing energy- building/repairing tissue in body

• Amino Acids- protein is made up of amino acids.- 20 standard amino acids

Introduction• Sequence

- string represent the primary structure of the protein

Primary structure

3D structure

Introduction• Homology Modeling refers to constructing an

model of the "target" protein from its amino acid sequence and/or an experimental 3D structure (the "template")

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Introduction• Homology Modeling

o When we want to know the 3D structure of a protein(target) that has not been solved

o You have only the sequence

o If there exist a solved experimental 3D structure(template) is similar to target protein

o We can use software to arrange the backbone of the sequence.

Model Production

Step 1 - Template Selection

Step 2 - Target-Template Alignment

Step 3 - Model Construction

Step 4 - Model Validation

Step 1. Template Selection

• First step in homology modeling is the identification of the best template structure.

• The simplest method of template identification relies on database search techniques such as BLAST. 

Step 1. Template Selection

• BLAST(Basic Local Alignment Search Tool)Input: sequenceOutput: templates with Identities, E-value …

Step 2. Target-Template Alignment• Comparison between target & template.

• Used to generate the model of protein.

Step 3. Model Construction

• Fragment assemblyrelied on the assembly of a complete model from

closely related solved structures.

• Segment matchingdivides the target into short segments, matched

to its own template fitted from the Protein Data Bank.

• Spatial restraint basedcommon software used is MODELLER.

Step 4. Model Validation

• An example:Tool: Errat

Model SelectionThe Protein Model Portal

• ModWeb• M4T• Swiss Model• I-TASSER• HHpred

PMP Work Flow

z

z

Swiss Model

Model SelectionServer Pdb files Model Name

Hhpred 1 (Chun)HHpred

I-TASSER 3 (Chun)I-TASSER model1 C-score=1.13(Chun)I-TASSER model2 C-score=-1.39(Chun)I-TASSER model3 C-score=0.70

M4T 1 (Chun)M4T

ModelWeb 2 (Chun)ModelWeb Model_fd(Chun)ModelWeb Model_f5

Swiss Model 1 (Chun)SwissModel

Model Selection

SequenceDifferentServer

pdb1

pdb2

pdb3

pdb4

pdb5

……

best pdb ?

Model SelectionModel Name Errat(overall

quality factor)

Verify 3D( percentage of the residues had an averaged 3D-1D score

> 0.2)

Prove(Z score)

(Chun)HHpred 86.856 93.52% 0.349

(Chun)I-TASSER model1 45.153 93.52% -0.075

(Chun)I-TASSER model2 48.329 77.31% 0.042

(Chun)I-TASSER model3 52.806 87.78% -0.176

(Chun)M4T 77.041 92.52% -0.137

(Chun)ModelWeb Model_fd

77.836 96.12% 0.050

(Chun)ModelWeb Model_f5

76.350 91.46% 1.196

(Chun)SwissModel 85.492 93.42% 0.302

Conclusion

• Homology modelingo Input sequence -> Template -> Build Model -> Validation

• Need understand and use tools well

• It cost time to validate model

Questions?