protein folding programs l.
Skip this Video
Loading SlideShow in 5 Seconds..
Protein Folding Programs PowerPoint Presentation
Download Presentation
Protein Folding Programs

Loading in 2 Seconds...

play fullscreen
1 / 19

Protein Folding Programs - PowerPoint PPT Presentation

  • Uploaded on

Protein Folding Programs. By Asım OKUR CSE 549 November 14, 2002. Protein Structure. DNA Sequence  Protein Sequence  Structure  (Mis)function It is believed that all the information necessary to determine the structure of a protein is present in its primary sequence.

I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
Download Presentation

PowerPoint Slideshow about 'Protein Folding Programs' - bob

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.

- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
protein folding programs

Protein Folding Programs



CSE 549

November 14, 2002

protein structure
Protein Structure
  • DNA Sequence  Protein Sequence  Structure  (Mis)function
  • It is believed that all the information necessary to determine the structure of a protein is present in its primary sequence.
protein folding programs3
Protein Folding Programs
  • Protein folding is one of the biggest computational challenges
  • Different types of folding and structure predictions programs
    • Simulations
    • Homology Modeling Approaches
  • Simulate the real behavior of proteins
  • High detail, short time scales
  • 2 main simulation types
    • Molecular Dynamics
    • Monte Carlo
the energy function
The Energy Function
  • Calculate energies for each particle
  • Since long range interactions important for each pair of particles the pair-wise interactions should be calculated
homology modeling
Homology Modeling
  • Template Selection and Fold Assignment
  • Target – Template Alignment
  • Model Building
    • Loop Modeling
    • Sidechain Modeling
  • Model Evaluation
fold assignment and template selection
Fold Assignment and Template Selection
  • Identify all protein structures with sequences related to the target, then select templates
  • 3 main classes of comparison methods
    • Compare the target sequence with each database sequence independently, pair-wise sequence – sequence comparison, BLAST and FASTA
    • Multiple sequence comparisons to improve sensitivity, PSI-BLAST
    • Threading or 3-D template matching methods
target template alignment
Target – Template Alignment
  • Most important step in Homology Modeling
  • A specialized method should be used for alignment
    • Over 40% identity the alignment is likely to be correct.
    • Regions of low local sequence similarity become common when overall sequence identity is under 40%. (Saqi et al., Protein Eng. 1999)
    • The alignment becomes difficult below 30% sequence identity. (Rost, Protein Eng. 1999)
model building
Model Building
  • Construct a 3-D model of the target sequence based on its alignment on template structures
  • Three different model building approaches
    • Modeling by rigid body assembly
    • Modeling by segment matching
    • Modeling by satisfaction of spatial restraints
  • Accuracies of these models are similar
  • Template selection and alignment have larger impact on the model

Screenshots from the Homology Modeling Server Swiss-Model

  • Construct a framework using known protein structures
  • Generate the location of the target amino acids on the framework
  • If loop regions not determined, additional database search or short simulations

Swiss-MOD Web Server


Procedure of the MODELLER program

  • After obtaining restraints run a geometry optimization or real-space optimization to satisfy them
errors in homology models
Errors in Homology Models
  • Errors in sidechain packing
  • Distortions and shifts in correctly aligned regions
  • Errors in regions without a template

d. Errors due to misalignment

e. Incorrect templates

  • Computer Simulations are powerful to show detailed motions but they cannot cover long enough time spans to simulate folding for large systems
  • Homology Modeling techniques can be successful if the target protein has a known fold
    • The higher the sequence similarity the more likely the model will be successful
    • With the implementation of better techniques the errors in fold assignment, alignment, and sidechain and loop modeling are decreasing
    • Theoretically, if at least one member of every possible fold is known, it is possible to predict the structure of every coding sequence to within a certain accuracy