Protein Structure Basics & Classification: Lecture 20 in BCB 444/544 Fall 07 - Prof. Drena, Lab Reports of Bioinformatics

Download Protein Structure Basics & Classification: Lecture 20 in BCB 444/544 Fall 07 - Prof. Drena and more Lab Reports Bioinformatics in PDF only on Docsity! #20 - Protein Structure Basics & Classification 10/8/07 BCB 444/544 Fall 07 Dobbs 1 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 1 BCB 444/544 Lecture 20 Protein Structure Basics, Visualization, Classification & Comparison #20_Oct08 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 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) 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 3 BCB 544 - Extra Required Reading Assigned Mon Sept 24 BCB 544 Extra Required Reading Assignment: for 544 Extra HW#1 Task 2 • Pollard KS, …., Haussler D. (2006) An RNA gene expressed during cortical development evolved rapidly in humans. Nature 443: 167-172. • http://www.nature.com/nature/journal/v443/n7108/abs/nature05113.html doi:10.1038/nature05113 • PDF available on class website - under Required Reading Link 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 4 BCB 544 Projects (Optional for BCB 444) • For a better idea about what's involved in the Team Projects, please look over last year's expectations for projects: http://www.public.iastate.edu/~f2007.com_s.544/project.htm • Criteria for evaluation of projects (oral presentations) are summarized here: http://www.public.iastate.edu/%7Ef2007.com_s.544/homework/HW7.pdf Please note: wrong URL (instead of that shown above) was included in originally posted 544ExtraHW#1; corrected version is posted now 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 5 Assignments & Announcements - #1 Students registered for BCB 444: Two Grading Options 1) Take Final Exam per original Grading Policies 2) Instead of taking Final Exam - you may participate in a Team Research Project If you choose #2, please do 3 things: 1) Contact Drena (in person) 2) Send email to Michael Terribilini (terrible@iastate.edu) 3) Complete 544 Extra HW#1 - Task 1.1 by noon on Mon Oct 1 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 6 Assignments & Announcements - #2 BCB 444s (Standard): 200 pts Midterm Exams = 100 points each 200 Homework & Laboratory assignments = 200 points 100 Final Exam 500 pts Total for BCB 444 BCB 444p (Project): 200 pts Midterm Exams = 100 points each 200 Homework & Laboratory assignments = 200 points 190 Team Research Project 590 pts Total for BCB 444p BCB 544: 200 pts Midterm Exams = 100 points each 200 Homework & Laboratory assignments 100 Final Exam 200 Discussion Questions & Team Research Projects 700 pts Total for BCB 544 #20 - Protein Structure Basics & Classification 10/8/07 BCB 444/544 Fall 07 Dobbs 2 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 7 Assignments & Announcements #3 ALL: HomeWork #3 Due: Mon Oct 8 (Today) 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 (not Monday) • 444 "Project-instead-of-Final" students should also submit: • HW544Extra #1 • Due: Task 1.1 - Mon Oct 8 (Today) by noon • Due: Task 1.2 - Fri Oct 12 by 5 PM (not Monday) Task 2 NOT required! 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 8 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) 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 9 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! 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 10 Amino Acids • Each of 20 different amino acids has different "R-Group" or side chain attached to Cα 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 11 Peptide Bond is Rigid and Planar 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 12 Certain Side-chain Configurations are Energetically Favored (Rotamers) Ramachandran plot: "Allowable" psi & phi angles #20 - Protein Structure Basics & Classification 10/8/07 BCB 444/544 Fall 07 Dobbs 5 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 25 Loops & Turns • Connect helices and sheets • Vary in length & 3-D configurations • Are located on surface of structure • Are more "tolerant" of mutations • Are more flexible, can adopt multiple conformations • Tend to have charged and polar amino acids • Are frequently components of active sites • Some fall into distinct structural families (e.g., hairpin loops, reverse turns) 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 26 Globular Proteins are Built from Recurring Structural Patterns • Structural Motifs & supersecondary structures = combinations of 2' structural elements • Domains = combinations of motifs • Independently folding unit (foldon) • Functional unit 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 27 Simple Motifs Combine to Form Domains 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 28 6 Main Classes of Protein Structure 1) α-Domains Bundles of helices connected by loops 2) β-Domains Mainly antiparallel sheets, usually with 2 sheets forming sandwich 3) α/β Domains Mainly parallel sheets with intervening helices, also 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 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 29 α-Domain Structures: 4-Helix Bundles 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 30 β-Sheets: Up-and-Down Sheets & Barrels #20 - Protein Structure Basics & Classification 10/8/07 BCB 444/544 Fall 07 Dobbs 6 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 31 α/β Domains: Leucine-rich Motifs can Form Horseshoes 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 32 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 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 33 PDB (RCSB) - recently "remediated" http://www.rcsb.org/pdb 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 34 Structure at NCBI http://www.ncbi.nlm.nih.gov/Structure 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 35 MMDB at NCBI http://www.ncbi.nlm.nih.gov/Structure/MMDB/mmdb.shtml 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 36 MMDB: Molecular Modeling Data Base • Derived from PDB structure records • "Value-added" to PDB records includes: • Integration with other ENTREZ databases & tools • Conversion to parseable ASN.1 data description language • Data also available in mmCIF & XML (also true for PDB now) • Correction of numbering discrepancies in structure vs sequence • Validation • Explicit chemical graph information (covalent bonds) • Integrated tool for identifying structural neighbors Vector Alignment Search Tool (VAST) #20 - Protein Structure Basics & Classification 10/8/07 BCB 444/544 Fall 07 Dobbs 7 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 37 MSD: Molecular Structure Database http://www.ebi.ac.uk/msd/ 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 38 wwPDB: World Wide PDB http://www.wwpdb.org 10/8/07BCB 444/544 F07 ISU Dobbs #20 - Protein Structure Basics & Classification 39 Chp 13 - Protein Structure Visualization, Comparison & Classification SECTION V STRUCTURAL BIOINFORMATICS Xiong: Chp 13 Protein Structure Visualization, Comparison & Classification • Protein Structural Visualization • Protein Structure Comparison • Protein Structure Classification