Homology modelling NMR Xray Homology Modelling Helices are
- Slides: 39
Homology modelling ? NMR ? X-ray ?
Homology Modelling !
Helices are Helices
Strands are Strands
Structure=Conservation
Structure=Conservation
Modelling beats X-ray
Data ~ infinite…
What can be Modelled ?
What can be Modelled ?
The ‘ 8’ Steps of Modelling 1 2 3 4 5 6 7 8 9 Detect template Get alignment Optimize template Exchange side chains Deal with insertions/deletions Optimize model Validate Iterate
The ‘ 8’ Steps of Modelling 1 2 3 4 5 6 7 8 9 Detect template Get alignment Optimize template Exchange side chains Deal with insertions/deletions Optimize model Validate Iterate
Template detection Normally BLAST is good enough. If BLAST doesn’t find a template, You should not want to build a model. When desperate, use PSI-BLAST (on PDB + Swiss. Prot), or use threading.
Threading means: Use information from the template structure to detect homology, or to improve an alignment.
Threading Small residues
Threading Alcoholic residues
Threading The folded ‘protein’
Threading Two aligned ‘proteins’
The ‘ 8’ Steps of Modelling 1 2 3 4 5 6 7 8 9 Detect template Get alignment Optimize template Exchange side chains Deal with insertions/deletions Optimize model Validate Iterate
Alignment Run BLAST on model sequence Run BLAST on template sequence Select 50 -100 representatives Do multiple sequence alignment Keep only model and template
How to align: ASASAS YPYPYP (three ways…)
How to align: ASASASAYAYAY-YPYPYP (two ways…)
The ‘ 8’ Steps of Modelling 1 2 3 4 5 6 7 8 9 Detect template Get alignment Optimize template Exchange side chains Deal with insertions/deletions Optimize model Validate Iterate
Alignment optimization 1 Use threading techniques. 2 Shift gaps around:
The ‘ 8’ Steps of Modelling 1 2 3 4 5 6 7 8 9 Detect template Get alignment Optimize template Exchange side chains Deal with insertions/deletions Optimize model Validate Iterate
Select ‘best’ template
Deal with errors
The ‘ 8’ Steps of Modelling 1 2 3 4 5 6 7 8 9 Detect template Get alignment Optimize template Exchange side chains Deal with insertions/deletions Optimize model Validate Iterate
Exchange side chains Keep template rigid Determine best rotamer Do NOT optimize rotamers If best rotamer doesn’t fit, start thinking. If the model is bad, you had the wrong template, or the wrong alignment. Make sure your model exists…
Position specific rotamers
Position specific rotamers
Position specific rotamers
The ‘ 8’ Steps of Modelling 1 2 3 4 5 6 7 8 9 Detect template Get alignment Optimize template Exchange side chains Deal with insertions/deletions Optimize model Validate Iterate
Insertions - Deletions Insertions are impossible Deletions: Move gap around in template till end point distance is short. If this is not possible, you have either the wrong template, or the wrong alignment.
The ‘ 8’ Steps of Modelling 1 2 3 4 5 6 7 8 9 Detect template Get alignment Optimize template Exchange side chains Deal with insertions/deletions Optimize model Validate Iterate
Model Optimization Do NOT use molecular dynamics:
Model Optimization Use 25 – 50 steps energy minimization, or use a force field that has been especially designed for the optimization of homology models.
The ‘ 8’ Steps of Modelling 1 2 3 4 5 6 7 8 9 Detect template Get alignment Optimize template Exchange side chains Deal with insertions/deletions Optimize model Validate Iterate
The ‘ 8’ Steps of Modelling 1 2 3 4 5 6 7 8 9 Detect template Get alignment Optimize template Exchange side chains Deal with insertions/deletions Optimize model Validate Iterate
- Insidan region jh
- Energy based model
- Homology modelling steps
- Homology modelling steps
- Microorganismos espirales
- Similarity vs homology
- Crustacea
- Homology and analogy difference
- Homology
- Homology is evidence of ______.
- Probability by homology
- Derived homology
- Biology homology
- Homology vs homoplasy
- Developmental homology
- Vestigial structures
- Homology definition biology
- Developmental homology
- Ap biology phylogenetic tree
- Mmc xray
- Subject contrast
- Capacitor-discharge mobile x-ray units
- Jfk skull
- Ellis curve on chest x ray
- Xray laser
- Scotch tape x ray
- Xray telescope
- Noi toi poi doi
- Croup xray steeple sign
- Emulsion peel x ray
- Who discovered x rays
- Rhese view xray
- Dr demeter judit
- Kub xray
- The xray guy
- Xray laser
- Pterigoid plate
- Xray searches
- Darkroom equipment in radiography
- Bacterial tracheitis xray