Protein Properties Function, structure Residue features Targeting Post-trans modifications BIO520 BioinformaticsJim Lund Reading: Chapter 11.1-3, 11.7,

Slides:

Advertisements

Similar presentations

Assignment of PROSITE motifs to topological regions: Application to a novel database of well characterised transmembrane proteins Tim Nugent.

Advertisements

Assignment of PROSITE motifs to topological regions: Application to a novel database of well characterised transmembrane proteins Tim Nugent 6 Month.

Secondary structure prediction from amino acid sequence.

Corrections. SEQUENCE 4 >seq4 MSTNNYQTLSQNKADRMGPGGSRRPRNSQHATASTPSASSCKEQQKDVEH EFDIIAYKTTFWRTFFFYALSFGTCGIFRLFLHWFPKRLIQFRGKRCSVE NADLVLVVDNHNRYDICNVYYRNKSGTDHTVVANTDGNLAELDELRWFKY.

Undergraduate Exercises with Trp Cage Paula Evans, Chet Fornari, Jeff Hansen, Jennifer Inlow, Larry Merkle.

Ch.5 Proteins: Primary structure Polypeptide diversity Protein purification and analysis Protein sequencing Protein evolution.

Review: Amino Acid Side Chains Aliphatic- Ala, Val, Leu, Ile, Gly Polar- Ser, Thr, Cys, Met, [Tyr, Trp] Acidic (and conjugate amide)- Asp, Asn, Glu, Gln.

©CMBI 2005 Exploring Protein Sequences - Part 2 Part 1: Patterns and Motifs Profiles Hydropathy Plots Transmembrane helices Antigenic Prediction Signal.

©CMBI 2005 Exploring Protein Sequences – Part 1 Part 1: Patterns and Motifs Profiles Hydropathy Plots Transmembrane helices Antigenic Prediction Signal.

© Wiley Publishing All Rights Reserved. Analyzing Protein Sequences.

Prediction of protein localization and membrane protein topology Gunnar von Heijne Department of Biochemistry and Biophysics Stockholm Bioinformatics Center.

CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU Homology Modeling Anne Mølgaard, CBS, BioCentrum, DTU.

Protein-a chemical view A chain of amino acids folded in 3D Picture from on-line biology bookon-line biology book Peptide Protein backbone N / C terminal.

1 Levels of Protein Structure Primary to Quaternary Structure.

An Introduction to Bioinformatics Protein Structure Prediction.

Sequence analysis June 18, 2008 Learning objectives-Understand the concept of sliding window programs. Understand difference between identity, similarity.

Thomas Blicher Center for Biological Sequence Analysis

©CMBI 2005 Why align sequences? Lots of sequences with unknown structure and function. A few sequences with known structure and function If they align,

CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU Homology Modelling Thomas Blicher Center for Biological Sequence Analysis.

PREDICTION OF PROTEIN FEATURES Beyond protein structure (TM, signal/target peptides, coiled coils, conservation…)

Protein Structure Elements Primary to Quaternary Structure.

A Genetic Approach to Analyzing Membrane Protein Topology Colin Manoil and Jon Beckwith Science, Vol. 233, , September 26, 1986.

PROTEIN SEQUENCE ANALYSIS. Need good protein sequence analysis tools because: As number of sequences increases, so gap between seq data and experimental.

Protein Bioinformatics Course

What are proteins? Proteins are important; e.g. for catalyzing and regulating biochemical reactions, transporting molecules, … Linear polymer chain composed.

Secondary Structure Prediction Protein Analysis Workshop 2008 Bioinformatics group Institute of Biotechnology University of helsinki Hung Ta

Protein Structure and Function 1 , 2 , 3 , 4  Structure Viewing, interpreting structure Protein Characterization BIO520 BioinformaticsJim Lund.

Levels of Protein Structure

Secondary Structure Prediction and Signal Peptides Protein Analysis Workshop 2012 Bioinformatics group Institute of Biotechnology University of helsinki.

Protein Secondary Structure Prediction. Input: protein sequence Output: for each residue its associated Secondary structure (SS): alpha-helix, beta-strand,

Day 2: Protein Sequence Analysis 1.Physico-chemical properties. 2.Cellular localization. 3.Signal peptides. 4.Transmembrane domains. 5.Post-translational.

Multiple Alignments Motifs/Profiles What is multiple alignment? HOW does one do this? WHY does one do this? What do we mean by a motif or profile? BIO520.

Department of Mechanical Engineering

Lecture 1: Fundamentals of Protein Structure

Secondary structure prediction

1 10/26/2015 MOLECULES. 2 10/26/2015 H 2 N-CH-C-OH O R Monomer E.g. protein Monomer vs polymer amino acid monomer R is a side group.

Exam I Review I. Several Amino Acids Occur Rarely in Proteins Figure 4.4 (c) Several amino acids that act as neurotransmitters and hormones.

Localization prediction of transmembrane proteins Stefan Maetschke, Mikael Bodén and Marcus Gallagher The University of Queensland.

The α-helix forms within a continuous strech of the polypeptide chain 5.4 Å rise, 3.6 aa/turn  1.5 Å/aa N-term C-term prototypical  = -57  ψ = -47 

es/by-sa/2.0/. From Protein Sequence to Protein Properties Prof:Rui Alves Dept Ciencies.

THE PUZZLING PROPERTIES OF THE PERMEASE (PPP) Kim Finer, Jennifer Galovich, Ruth Gyure, Dave Westenberg March 4, 2006.

Amino acids structure. Configuration of Amino Acids.

School B&I TCD Bioinformatics Proteins: structure,function,databases,formats.

Protein Modeling Protein Structure Prediction. 3D Protein Structure ALA CαCα LEU CαCαCαCαCαCαCαCα PRO VALVAL ARG …… ??? backbone sidechain.

Introduction to Protein Structure Prediction BMI/CS 576 Colin Dewey Fall 2008.

Amino Acids ©CMBI 2001 “ When you understand the amino acids, you understand everything ”

Alignment & Secondary Structure You have learned about: Data & databases Tools Amino Acids Protein Structure Today we will discuss: Aligning sequences.

Russell Group, Protein Evolution _________ ____ Rob Russell Cell Networks University of Heidelberg Interactions and Modules: the how and why of molecular.

Hyperthermophile subtilases

Protein Structure and Bioinformatics. Chapter 2 What is protein structure? What are proteins made of? What forces determines protein structure? What is.

Bioinformatics in Vaccine Design

Protein backbone Biochemical view:

Levels of Protein Structure. Why is the structure of proteins (and the other organic nutrients) important to learn?

V2 SS 2009 Membrane Bioinformatics 1 V2 - Predicting TM helices from sequence Review % of all genes code for transmembrane proteins (1) High energetic.

Marlou Snelleman 2012 Protein structure. Overview Sequence to structure Hydrogen bonds Helices Sheets Turns Hydrophobicity Helices Sheets Structure and.

Protein structure, domains, and interactions Curtis Huttenhower Harvard T.H. Chan School of Public Health Department of Biostatistics.

EBI is an Outstation of the European Molecular Biology Laboratory. A web based integrated search service to understand ligand binding and secondary structure.

Protein Structure Prediction. Protein Sequence Analysis Molecular properties (pH, mol. wt. isoelectric point, hydrophobicity) Secondary Structure Super-secondary.

Protein structure depends on amino acid sequence and interactions Amino acid sequence Local interactions Long distance interactions Interactions between.

Prediction of protein features. Beyond protein structure

Bio/Chem-informatics

Protein Families, Motifs & Domains.

Conservation of Structure and Mechanism between Eukaryotic Topoisomerase I and Site-Specific Recombinases Chonghui Cheng, Paul Kussie, Nikola Pavletich,

Protein Bioinformatics Course

Protein Structure Prediction

Volume 16, Issue 4, Pages (April 2008)

Protein structure prediction.

Alignment of N-terminal sequences of type IV pilin proteins.

Three protein kinase structures define a common motif

Structural features of seven streptococcal cell surface proteins that function in adherence and colonization. Structural features of seven streptococcal.

Presentation transcript:

Protein Properties Function, structure Residue features Targeting Post-trans modifications BIO520 BioinformaticsJim Lund Reading: Chapter , 11.7, 12.1, Ch 14

Protein function, structure Homology to known proteins through protein search and alignment Functional domains –NCBI CDD (conserved domain database) –Interpro (PROSITE, Pfam, SMART, etc.)

Simple Analyses Composition (#’s of each aa) Isoelectric point Extinction co-efficient Peptide cleavage Repetitive regions ExPASy, BCM Search Launcher, other sites.

CDD domains in Insulin-Like Growth Factor Receptor

Composition (Peptide) COMPOSITION of: (Human glyceraldehyde-3- phosphate dehydrogenase) *.pep Check: 5354 from: 1 to: 334 October 6, :18 ***** A: 33 C: 3 D: 23 E: 16 F: 15 G: 34 H: 10 I: 21 K: 27 L: 20 M: 9 N: 13 P: 11 Q: 4 R: 10 S: 20 T: 21 V: 32 W: 3 Y: 9 Other: 0 Total: 334

Isoelectric Point(pI) Number of Hydrogen Ions Bound Net pH Arg Lys His Tyr Cys Glu Asp NH2 COOH Total Charge

Extinction co-efficient S-S SH 1  g/ml Used for determining protein concentration. Based on number C, Y, and W residues.

PeptideMap PeptideSort Cleave polypeptide with proteases, reagents Predict HPLC properties of peptide fragments

Protein Analyses Secondary Structure Prediction Hydrophobicity/membrane insertion Antigenicity Surface Accessibility Baylor Search Launcher: predict.html ExPASy:

Secondary Structure Prediction Amino acid preferences Local aa interactions Non-local interactions Homology/Multiple alignments

Predict H, E, L (Helix, B-strand, Loop) ~75% aa accuracy Programs –APSSP –Jpred –PHDsec –SAM-T99 –PredictProtein Web sites –BCM Search Launcher –ExPASy Tools Secondary Structure Prediction

Membrane Association Hydropathy, Hydophobicity –  G transfer (water-vapor) –% sidechains buried (100% or 95%) Identify membrane-associated regions Identify membrane-spanning regions (>16 aa, ~80 Å helix)

Hydrophobicity Membrane Topology Original paper: Kyte-Doolittle –J. Mol. Biol. (1978) 157: Further refinements: Hopp-Woods –Proc Natl Acad Sci U S A (1981) 78:3824 Gunnar von Heijne GES-scale (Goldman, Engelman, Steitz) –Engelman et al, 1982

SOAP (Kyte-Doolittle) Plots

Membrane Topology Hydrophobic helices Dipoles aligned Charges? What is the overall structure? External and internal domains?

Localization Signal sequences direct proteins –Usually N or C terminal signal sequences Targeted to: membrane, secretion, nucleus, mitochondria, chloroplast, lysosome, peroxisome, periplasm Program criteria: N-term motifs, aa composition, protein domains specific to locations, homology to proteins with experimentally determined locations. Accuracy varies with type of prediction, 50-80% Programs: –WoLF PSORT (eukaryotic), PSORTb (bacterial), PSORT (plant) –SUBLOC –TargetP

Surface Accessibility Emini et al (1985) 55:836 Can also calculate (for real) on a PDB structure via WWW heidelberg.de/ASC/scr1-form.html

Antigenicity Jameson and Wolf (CABIOS 4:181) –Sums secondary structure indices, surface accessibility, backbone flexibility –Many good epitopes are linear, surface loops Used when “picking” antigenic peptides

Transmembrane segment prediction Hydrophobicity Membrane association/topology Programs –PHDhtm –TopPred –TMHMM