16-10-2010, 10:37 AM
unit 5.ppt (Size: 3.72 MB / Downloads: 161)
Prediction of protein conformations from protein sequences
Protein Conformations
Predict protein 3D structure from (amino acid) sequence
Sequence ® secondary structure ® 3D structure ® function
Protein 3D Structure Detection
X-ray Crys
NMR
Expensive
Slow
Protein Structure
Protein 3D structure → biological function
Lock & key model of enzyme function (docking)
Folding problem
protein sequence Û 3D structure
Structure prediction and alignment
Protein design, drug design, etc …
The “holy grail” of bioinformatics
The Prediction Problem
Can we predict the final 3D protein structure knowing only its amino acid sequence?
Studied for 4 Decades
Primary Motivation for Bioinformatics
Based on this 1-to-1 Mapping of Sequence to Structure
Still very much an OPEN PROBLEM
Predicting Protein Structure
Goal
Find best fit of sequence to 3D structure
Comparative (homology) modeling (同源建模法)
Construct 3D model from alignment to protein sequences with known structure
Threading (fold recognition) (折叠识别法)
Pick best fit to sequences of known 2D / 3D structures (folds)
Ab initio / de novo methods (从头预测法)
Attempt to calculate 3D structure “from scratch”
Molecular dynamics
Energy minimization
Lattice models