Protein Structure Prediction and Analysis. 1. Protein Structure Prediction - Homology Modeling,...
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- Slide 1
- Protein Structure Prediction and Analysis
- Slide 2
- 1. Protein Structure Prediction - Homology Modeling, Threading,
Ab Initio Structure Prediction 2. Protein Structure Evaluation 3.
Protein Structure Comparison - DSSP, PROCHECK, VADAR, Verify 3D -
Structure superposition, RMSD, CATH, SCOP Contents
- Slide 3
- Protein Structure Prediction 1. Homology Modeling 2. Threading
(fold recognition) 3. Ab Initio Structure Prediction
- Slide 4
- 1. Homology Modeling ; The most powerful and accurate approach
Predicting three-dimensional structures of proteins based on the
coordinates of known homologs founds in PDB. Homology modeling by
multi-step process that sequencing alignment, structure
modification database searches, energy minimization and structure
evaluation to generate a structure. Download program : Modeller,
DeepView, WHATEIF Web-accessible services : SWISS-MODEL, CPH
Models, SDSC1 The most critical step is the first step-alignment
alignmentreplacing backbone segments replacing side chain refining
the model validating the model
- Slide 5
- Homology Modeling
- Slide 6
- E.Coli thioredoxin Human thioredoxin 26 % sequence
identity
- Slide 7
- 2. Threading ( fold recognition) Web-accessible services :
SAMt99, three-dimensional-PSSM, FUGUE, metaservers ; Predicting the
structure, or recognizing a common fold in proteins Two approaches
to threading exist. - DBM (distance-based method):
three-dimensional threading - PBM (prediction-based method):
two-dimensional threading 3. Ab Initio Structure Prediction ;
Predicting protein structures without prior knowledge of any
three-dimensional structure. ab inito structure prediction program
: ROSETTA
- Slide 8
- Threading ( fold recognition) Fig 9.10 A schematic illustration
of how threading is performed.
- Slide 9
- Protein Structure Evaluation ; A high-quality structure can
reveal a tremendous amount of biologically important information -
Testing new hypotheses on folding or function - The basis to design
and construct mutant, or to design new drug How good is this
protein structure ? There are some near-universal characteristics
to high-quality structures. These observations have led to the
development of a number of excellent software programs for
automatically evaluating protein structures and protein models
- Slide 10
- Protein Structure Evaluation 1. DSSP 3. VADAR 4. Verify 3D 2.
PROCHECK Dictionary of Secondary Structure for Protein A very
stringent method to identify hydrogen bonds and hydrogen bonding
patterns Determination of the accessible surface area of individual
residues using the ANAREA algorithm
- Slide 11
- Protein Structure Evaluation 1. DSSP 3. VADAR 4. Verify 3D 2.
PROCHECK The first quantitative protein structure evaluation
program and one of the best available. Accepts PDB coordinate files
as input and uses DSSP Most appealing features is its colorful
graphical reports along with tables, explanation, and
references
- Slide 12
- Protein Structure Evaluation 1. DSSP 3. VADAR 4. Verify 3D 2.
PROCHECK The Volume, Area, Dihedral Angle Reporter is a fully
Web-enable protein structure evaluation tool. VADAR uses a more
comprehensive approach to identifying secondary structures. VADAR
offers a very comprehensive and highly informative picture of
protein structure.
- Slide 13
- Protein Structure Evaluation 1. DSSP 3. VADAR 4. Verify 3D 2.
PROCHECK Verify3D uses a form of three-dimensional threading to
evaluation protein structure aquality. Verify3D uses a matrix
scoring method in which the secondary structure and solvent
exposure propensity of each of the 20 a. a was determined
statiscally. Low values ( 0.5) : structure is good.
- Slide 14
- Protein Structure Comparison ; Structure comparison can provide
tremendous insight into the origin, function, location,
interactions, and activity of protein. Structure comparison is a
much more computationally difficult process than seq comparison The
most common method is called structure superposition. Web server :
SuperPose, ProSup PDB coordinate list, information on the
alignment, number of equivalent residues, RMSD
- Slide 15
- RMSD (root mean square deviation) ; In the case of structure
comparisons, these are scored using RMSD. RMSD is calculated the
same way a standard deviation is calculated. RMSD( ) = d 1 2 + d 2
2 +/ n
- Slide 16
- Protein Structure Comparison 1. CATH 2. SCOP 3. DALI, CE, VAST
; The CATH database can be searched by in a PDB accession number to
see the Class, Architecture, Topology, and Homologous superfamily
to which a protein belongs. ; These servers simply perform strucure
comparisons and automatically group structure families using
well-defined mathematical criteria. ; The SCOP database is a
similar hierarchically structure database providing a slightly
different taxonomic partitioning. (Class, Fold, Family and
Superfamily)
- Slide 17
- Figure 9.13 An example of the CATH database description of
E.coli thioredoxin.