Protein Secondary Structure Prediction - Prof. Drena Leigh Dobbs, Lab Reports of Bioinformatics

Download Protein Secondary Structure Prediction - Prof. Drena Leigh Dobbs and more Lab Reports Bioinformatics in PDF only on Docsity! #21 - Protein Secondary Structure Prediction 10/10/07 BCB 444/544 Fall 07 Dobbs 1 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 1 BCB 444/544 Lecture 21 Protein Structure Visualization, Classification & Comparison  Secondary Structure Prediction #21_Oct10 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 2 Mon Oct 8 - Lecture 20 Protein Secondary Structure Prediction • Chp 14 - pp 200 - 213 Wed Oct 10 - Lecture 21 Protein Tertiary Structure Prediction • Chp 15 - pp 214 - 230 Thurs Oct 11 & Fri Oct 12 - Lab 7 & Lecture 22 Protein Tertiary Structure Prediction • Chp 15 - pp 214 - 230 Required Reading (before lecture) 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 3 Assignments & Announcements ALL: HomeWork #3 √ Due: Mon Oct 8 by 5 PM • HW544: HW544Extra #1 √ Due: Task 1.1 - Mon Oct 1 by noon Due: Task 1.2 & Task 2 - Fri Oct 12 by 5 PM • 444 "Project-instead-of-Final" students should also submit: • HW544Extra #1 • √ Due: Task 1.1 - Mon Oct 8 by noon •Due: Task 1.2 - Fri Oct 12 by 5 PM <Task 2 NOT required for BCB444 students> 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 4 Seminars this Week - Thurs: BCB List of URLs for Seminars related to Bioinformatics: http://www.bcb.iastate.edu/seminars/index.html • Oct 11 Thurs • Dr. Klaus Schulten (Univ of Illinois) - Baker Center Seminar The Computational Microscope 2:10 PM in E164 Lagomarcino http://www.bioinformatics.iastate.edu/seminars/abstracts/2007_2008/ Klaus_Schulten_Seminar.pdf • Dr. Dan Gusfield (UC Davis) - Computer Science Colloquium ReCombinatorics: Combinatorial Algorithms for Studying History of Recombination in Populations 3:30 PM in Howe Hall Auditorium http://www.cs.iastate.edu/~colloq/new/gusfield.shtml 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 5 Seminars this Week - Fri: BCB List of URLs for Seminars related to Bioinformatics: http://www.bcb.iastate.edu/seminars/index.html • Oct 12 Fri • Dr. Edward Yu (Physics/BBMB, ISU) - BCB Faculty Seminar TBA: "Structural Biology" (see URL below) 2:10 PM in 102 Sci http://webdev.its.iastate.edu/webnews/data/site_gdcb_dept_seminars/30/webne wsfilefield_abstract/Dr.-Ed-Yu.pdf • Dr. Srinivas Aluru (ECprE, ISU) - GDCB Seminar Consensus Genetic Maps: A Graph Theoretic Approach 4:10 PM in 1414 MBB http://webdev.its.iastate.edu/webnews/data/site_gdcb_dept_seminars/35/web newsfilefield_abstract/Dr.-Srinivas-Aluru.pdf 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 6 Chp 12 - Protein Structure Basics SECTION V STRUCTURAL BIOINFORMATICS Xiong: Chp 12 Protein Structure Basics • Amino Acids • Peptide Bond Formation • Dihedral Angles • Hierarchy • Secondary Structures • Tertiary Structures • Determination of Protein 3-Dimensional Structure • Protein Structure DataBank (PDB) #21 - Protein Secondary Structure Prediction 10/10/07 BCB 444/544 Fall 07 Dobbs 2 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 7 Protein Structure & Function • Protein structure - primarily determined by sequence • Protein function - primarily determined by structure • Globular proteins: compact hydrophobic core & hydrophilic surface • Membrane proteins: special hydrophobic surfaces • Folded proteins are only marginally stable • Some proteins do not assume a stable "fold" until they bind to something = Intrinsically disordered  Predicting protein structure and function can be very hard -- & fun! 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 8 6 Main Classes of Protein Structure 1) α-Domains Bundles of helices connected by loops 2) β-Domains Mainly antiparallel sheets, usually 2 sheets forming sandwich 3) α/β Domains Mainly parallel sheets with intervening helices, mixed sheets 4) α+β Domains Mainly segregated helices and sheets 5) Multidomain (α & β) Containing domains from more than one class 6) Membrane & cell-surface proteins 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 9 Protein Structure Databases PDB - Protein Data Bank http://www.rcsb.org/pdb/ (RCSB) - THE protein structure database MMDB - Molecular Modeling Database http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure (NCBI Entrez) - has "added" value MSD - Molecular Structure Database http://www.ebi.ac.uk/msd Especially good for interactions & binding sites 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 10 PDB (RCSB) - recently "remediated" http://www.rcsb.org/pdb 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 11 Structure at NCBI http://www.ncbi.nlm.nih.gov/Structure 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 12 MMDB at NCBI http://www.ncbi.nlm.nih.gov/Structure/MMDB/mmdb.shtml #21 - Protein Secondary Structure Prediction 10/10/07 BCB 444/544 Fall 07 Dobbs 5 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 25 Protein Structure Classification • SCOP = Structural Classification of Proteins Levels reflect both evolutionary and structural relationships http://scop.mrc-lmb.cam.ac.uk/scop • CATH = Classification by Class, Architecture,Topology & Homology http://cathwww.biochem.ucl.ac.uk/latest/ • DALI - (recently moved to EBI & reorganized) DALI Database (fold classification) http://ekhidna.biocenter.helsinki.fi/dali/start Each method has strengths & weaknesses…. 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 26 SCOP - Structure Classification http://scop.mrc-lmb.cam.ac.uk/scop/ 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 27 CATH - Structure Classification http://www.cathdb.info/latest/index.html 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 28 Chp 14 - Secondary Structure Prediction SECTION V STRUCTURAL BIOINFORMATICS Xiong: Chp 14 Protein Secondary Structure Prediction • Secondary Structure Prediction for Globular Proteins • Secondary Structure Prediction for Transmembrane Proteins • Coiled-Coil Prediction 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 29 Secondary Structure Prediction Has become highly accurate in recent years (>85%) • Usually 3 (or 4) state predictions: • H = α-helix • E = β-strand • C = coil (or loop) • (T = turn) 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 30 Secondary Structure Prediction Methods • 1st Generation methods Ab initio - used relatively small dataset of structures available Chou-Fasman - based on amino acid propensities (3-state) GOR - also propensity-based (4-state) • 2nd Generation methods based on much larger datasets of structures now available GOR II, III, IV, SOPM • 3rd Generation methods Homology-based & Neural network based PHD, PSIPRED, SSPRO, PROF, HMMSTR • Meta-Servers combine several different methods Consensus & Ensemble based JPRED, PredictProtein #21 - Protein Secondary Structure Prediction 10/10/07 BCB 444/544 Fall 07 Dobbs 6 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 31 Secondary Structure Prediction Servers Prediction Evaluation? • Q3 score - % of residues correctly predicted (3-state) in cross-validation experiments Best results? Meta-servers • http://expasy.org/tools/ (scroll for 2' structure prediction) • http://www.russell.embl-heidelberg.de/gtsp/secstrucpred.html • JPred www.compbio.dundee.ac.uk/~www-jpred • PredictProtein http://www.predictprotein.org/ Rost, Columbia Best individual programs? ?? • CDM http://gor.bb.iastate.edu/cdm/ Sen…Jernigan, ISU • GOR V http://gor.bb.iastate.edu/ Kloczkowsky…Jernigan, ISU 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 32 • Developed by Jernigan Group at ISU • Basic premise: combination of 2 complementary methods can enhance performance by harnessing distinct advantages of both methods; combines FDM & GOR V: • FDM - Fragment Data Mining - exploits availability of sequence- similar fragments in the PDB, which can lead to highly accurate prediction - much better than GOR V - for such fragments, but such fragments are not available for many cases • GOR V - Garnier, Osguthorpe, Robson V - predicts secondary structure of less similar fragments with good performance; these are protein fragments for which FDM method cannot find suitable structures • For references & additional details: http://gor.bb.iastate.edu/cdm/ Consensus Data Mining (CDM) 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 33 Secondary Structure Prediction: for Different Types of Proteins/Domains For Complete proteins: Globular Proteins - use methods previously described Transmembrane (TMM) Proteins - use special methods (next slides) For Structural Domains: many under development: Coiled-Coil Domains (Protein interaction domains) Zinc Finger Domains (DNA binding domains), others… 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 34 SS Prediction for Transmembrane Proteins Transmembrane (TM) Proteins • Only a few in the PDB - but ~ 30% of cellular proteins are membrane-associated ! • Hard to determine experimentally, so prediction important • TM domains are relatively 'easy' to predict! Why? constraints due to hydrophobic environment 2 main classes of TM proteins: α- helical β- barrel 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 35 SS Prediction for TM α-Helices α-Helical TM domains: • Helices are 17-25 amino acids long (span the membrane) • Predominantly hydrophobic residues • Helices oriented perpendicular to membrane • Orientation can be predicted using "positive inside" rule Residues at cytosolic (inside or cytoplasmic) side of TM helix, near hydrophobic anchor are more positively charged than those on lumenal (inside an organelle in eukaryotes) or periplasmic side (space between inner & outer membrane in gram-negative bacteria) • Alternating polar & hydrophobic residues provide clues to interactions among helices within membrane Servers? • TMHMM or HMMTOP - 70% accuracy - confused by hydrophobic signal peptides (short hydrophobic sequences that target proteins to the endoplasmic reticulum, ER) • Phobius - 94% accuracy - uses distinct HMM models for TM helices & signal peptide sequences 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 36 SS Prediction for TM β-Barrels β-Barrel TM domains: • β-strands are amphipathic (partly hydrophobic, partly hydrophilic) • Strands are 10 - 22 amino acids long • Every 2nd residue is hydrophobic, facing lipid bilayer • Other residues are hydrophilic, facing "pore" or opening Servers? Harder problem, fewer servers… TBBPred - uses NN or SVM (more on these ML methods later) Accuracy ? #21 - Protein Secondary Structure Prediction 10/10/07 BCB 444/544 Fall 07 Dobbs 7 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 37 Prediction of Coiled-Coil Domains Coiled-coils • Superhelical protein motifs or domains, with two or more interacting α-helices that form a "bundle" • Often mediate inter-protein (& intra-protein) interactions 'Easy' to detect in primary sequence: • Internal repeat of 7 residues (heptad) • 1 & 4 = hydrophobic (facing helical interface) • 2,3,5,6,7 = hydrophilic (exposed to solvent) • Helical wheel representation - can be used manually detect these, based on amino acid sequence Servers? Coils, Multicoil - probability-based methods 2Zip - for Leucine zippers = special type of CC in TFs: characterized by Leu-rich motif: L-X(6)-L-X(6)-L-X(6)-L 10/10/07BCB 444/544 F07 ISU Dobbs #21 - Protein Secondary Structure Prediction 38 Chp 15 - Tertiary Structure Prediction SECTION V STRUCTURAL BIOINFORMATICS Xiong: Chp 15 Protein Tertiary Structure Prediction • Methods • Homology Modeling • Threading and Fold Recognition • Ab Initio Protein Structural Prediction • CASP