Protein Folding Applications

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Protein Folding Applications
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CASP

• Biannual protein structural prediction
  competition
• Metric root mean square
• In the range of 2-6 Å

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Prediction Tools

• 3 categories of structural prediction tools
• Comparative modeling
• Homology
• Fold recognition
• Base on a library of known protein folds
• Ab initio prediction
• Use first principles (energy minimization, MC)

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Goals

• Address the following questions about the current
  state of the art in protein structure prediction
  
• Are the models produced similar to the
  corresponding experimental structure?
• Are the details of the models correct?
• Has there been progress from the earlier CASPs?
• What methods are most effective?
• Where can future effort be most productively
  focused?

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Successful Ab Initio prediction
experiment
CASP4 target 102 Solution Structure Of
Bacteriocin As-48
CA RMS 4.02 angstrom
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Successful Ab Initio predictions of fold topology
CASP4 target 97 Erp29 C-Domain
experiment
CA RMS 9.21 angstrom
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T128 - 203 residues Manganese superoxide
dismutase homolog
0.928 A CA RMSD
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T123 - 160 residues Beta-lactoglobulin
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(No Transcript)
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Lyase With Bound Product
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Lyase With Bound Product
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BLUE - Model - T0086TS384_1
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Largest set of residues from the Model
T0086TS384_1 that can fit under DISTANCE cutoff
5 percent of residues ( 8 residues ) fits under
1A with local RMSD   0.55 10 percent of residues
( 17 residues ) fits under 2A with local RMSD  
1.49 22 percent of residues ( 36 residues ) fits
under 4A with local RMSD   2.80 31 percent of
residues ( 51 residues ) fits under 6A with local
RMSD   3.69 Percent of the structure predicted
100.00  
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BLUE - Model - T0086AL104_1
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Largest set of residues from the Model
T0086AL104_1 that can fit under DISTANCE cutoff
5 percent of residues ( 8 residues ) fits under
1A with local RMSD   0.45 6 percent of residues
( 10 residues ) fits under 2A with local RMSD  
1.39 9 percent of residues ( 15 residues ) fits
under 4A with local RMSD   2.56 13 percent of
residues ( 22 residues ) fits under 6A with local
RMSD   4.49 Percent of the structure predicted
84.15   ( CA atoms   Model 138 , Target 164 )
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CASP5

• The prediction season is planned to start in May
  and end in August.
• Asilomar Conference Center in Pacific Grove near
  Monterey, California.
• December 1st - 5th, 2002

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From Basic to Applied Research

• Rational drug design
• AIDS therapy
• The cocktail drug was made possible because of
  the use of molecular modeling
• Treatment for blood coagulation
• Thrombin inhibitors were also designed though the
  use of molecular modeling