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Protein Structure Prediction and Analysis1. Protein Structure Prediction- Homology Modeling, Threading, Ab Initio Structure Prediction2. Protein Structure Evaluation3. Protein Structure Comparison- DSSP, PROCHECK, VADAR, Verify 3D - Structure superposition, RMSD, CATH, SCOP

ContentsProtein Structure Prediction1. Homology Modeling2. Threading (fold recognition) 3. Ab Initio Structure Prediction1. Homology Modeling; The most powerful and accurate approachPredicting 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, WHATEIFWeb-accessible services : SWISS-MODEL, CPH Models, SDSC1The most critical step is the first step-alignmentalignment replacing backbone segments replacing side chain refining the model validating the model

Homology Modeling

E.Coli thioredoxinHuman thioredoxin26 % sequence identity2. Threading ( fold recognition)Web-accessible services : SAMt99, three-dimensional-PSSM, FUGUE, metaservers; Predicting the structure, or recognizing a common fold in proteinsTwo approaches to threading exist.- DBM (distance-based method): three-dimensional threading- PBM (prediction-based method): two-dimensional threading3. Ab Initio Structure Prediction; Predicting protein structures without prior knowledge of any three-dimensional structure. ab inito structure prediction program : ROSETTA

Threading ( fold recognition)Fig 9.10 A schematic illustration of how threading is performed.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 modelsProtein Structure Evaluation1. DSSP3. VADAR4. Verify 3D2. PROCHECKDictionary of Secondary Structure for ProteinA very stringent method to identify hydrogen bonds and hydrogen bonding patternsDetermination of the accessible surface area of individual residues using the ANAREA algorithmProtein Structure Evaluation1. DSSP3. VADAR4. Verify 3D2. PROCHECKThe first quantitative protein structure evaluation program and one of the best available.Accepts PDB coordinate files as input and uses DSSPMost appealing features is its colorful graphical reports along with tables, explanation, and referencesProtein Structure Evaluation1. DSSP3. VADAR4. Verify 3D2. PROCHECKThe 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.Protein Structure Evaluation1. DSSP3. VADAR4. Verify 3D2. PROCHECKVerify3D 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.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 comparisonThe most common method is called structure superposition.

Web server : SuperPose, ProSup PDB coordinate list, information on the alignment, number of equivalent residues, RMSD

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() = d12+ d22+/ nProtein Structure Comparison1. CATH2. SCOP3. 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)

Figure 9.13 An example of the CATH database description of E.coli thioredoxin.