Details of Protein Structure

Size: px
Start display at page:

Download "Details of Protein Structure"

Transcription

1 Details of Protein Structure Function, evolution & experimental methods Thomas Blicher, Center for Biological Sequence Analysis Anne Mølgaard, Kemisk Institut, Københavns Universitet

2 Learning Objectives Outline the basic levels of protein structure. Outline key differences between X-ray crystallography and NMR spectroscopy. Identify relevant parameters for evaluating the quality of protein structures determined by X-ray crystallography and NMR spectroscopy.

3 Outline Protein structure evolution and function Inferring function from structure. Modifying function Experimental techniques X-ray crystallography NMR spectroscopy Structure validation

4 Watson, Crick and DNA, 1952

5 DNA Conclusions "We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest. It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." J.D. Watson & F.H.C. Crick (1953) Nature, 171, 737.

6 Once Upon a Time Could the search for ultimate truth really have revealed so hideous and visceral-looking an object? Max Perutz, 1964, on protein structure John Kendrew, 1959, with myoglobin model

7 Why are Protein Structures so Interesting? They provide a detailed picture of interesting biological features, such as active site, substrate specificity, allosteric regulation etc. They aid in rational drug design and protein engineering. They can elucidate evolutionary relationships undetectable by sequence comparisons.

8 Structure & Evolution In evolution structure is conserved longer than both function and sequence. Structure > Function > Sequence

9 Structure & Evolution Rhamnogalacturonan acetylesterase (A. aculeatus) (1k7c) Platelet activating factor acetylhydrolase (B. Taurus) (1WAB) Serine esterase (S. scabies) (1ESC)

10 Structure to Function Inferring biological features from the structure 1DEO NH 2 Asp His Ser Topological switchpoint COOH

11 Structure & Evolution Rhamnogalacturonan acetylesterase Serine esterase Platelet activating factor acetylhydrolase Mølgaard, Kauppinen & Larsen (2000) Structure, 8,

12 Why Fold? Hydrophobic collapse Hydrophobic residues cluster to escape interactions with water. Indirect effect of attraction between water molecules. Polar backbone groups form secondary structure to satisfy hydrogen bonding donors and acceptors. Interactions with Initially formed structure is in molten globule state (ensemble). Molten globule condenses to native fold via transition state

13 Hydrophobic Effect and Folding Oil and water Clathrate structures Entropy Indirect consequence of attraction between water molecules

14 Hydrophobic Core Hydrophobic side chains go into the core of the molecule but the main chain is highly polar. The polar groups (C=O and NH) are neutralized through formation of H-bonds. Myoglobin Surface Interior

15 Hydrophobic vs. Hydrophilic Globular protein (in solution) Membrane protein (in membrane) Myoglobin Aquaporin

16 Hydrophobic vs. Hydrophilic Globular protein (in solution) Membrane protein (in membrane) Cross-section Myoglobin Cross-section Aquaporin

17 Characteristics of Helices Aligned peptide units Dipolar moment Ion/ligand binding Secondary and quaternary structure packing Capping residues The helix (i i+4) Other helix types! (3 10, ) C N

18 -Sheets Multiple strands sheet Parallel vs. antiparallel Twist Thioredoxin Flexibility Vs. helices Folding Structure propagation (amyloids) Other

19 -Sheets Multiple strands sheet Parallel vs. antiparallel Twist Flexibility Vs. helices Folding Structure propagation (amyloids) Other

20 -Sheets Multiple strands sheet Parallel vs. antiparallel Twist Flexibility Vs. helices Folding Structure propagation (amyloids) Other

21 -Sheets Multiple strands sheet Parallel vs. antiparallel Twist Flexibility Vs. helices Folding Structure propagation (amyloids) Other

22 -Sheets Multiple strands sheet Parallel vs. antiparallel Twist Antiparallel Parallel Strand interactions are non-local Flexibility Vs. helices Folding

23 Turns, Loops & Bends Revisited Between helices and sheets On protein surface Intrinsically unstructured proteins

24 Structure Levels Primary structure = Sequence Secondary Structure = Helix, sheets/strands, loops & turns Structural Motif = Small, recurrent arrangement of secondary structure, e.g. Helix-loop-helix Beta hairpins EF hand (calcium binding motif) Etc. MSSVLLGHIKKLEMGHS Tertiary structure = Arrangement of Secondary structure elements

25 Quaternary Structure Assembly of monomers/subunits into protein complex Backbone-backbone, backbone-side-chain & side-chain-side-chain interactions: Intramolecular vs. intermolecular contacts. For ligand binding side chains may or may not contribute. For the latter, mutations have little effect. Myoglobin Hemoglobin

26 Grouping Amino Acids A Ala C Cys D Asp E Glu F Phe G Gly H His I Ile K Lys L Leu M Met N Asn P Pro Q Gln R Arg S Ser T Thr V Val W Trp Y - Tyr Livingstone & Barton, CABIOS, 9, , 1993

27

28 Proteins Are Polypeptides The peptide bond A polypeptide chain

29 Ramachandran Plot Allowed backbone torsion angles in proteins N H

30 Torsion Angles

31 Ramachandran Plots

32 Engineering Thermostability Example: Serpin (serine protease inhibitor) Overpacking Buried polar groups Cavities Im, Ryu & Yu (2004) Engineering thermostability in serine protease inhibitors PEDS, 17,

33 Experimental Methods Crystallography & NMR spectroscopy

34 Methods for Structure Determination X-ray crystallography Nuclear Magnetic Resonance (NMR) Modelling techniques More exotic techniques Cryo electron microscopy (Cryo EM) Small angle X-ray scattering (SAXS) Neutron scattering

35 X-ray Crystallography No size limitation. Protein molecules are stuck in a crystal lattice. Some proteins seem to be uncrystallizable. Slow. Especially suited for studying structural details.

36 X-rays Fourier transform

37 The Importance of Resolution 4 Å low 3 Å 2 Å 1 Å high

38 Key Parameters Resolution R values Agreement between data and model. Usually between 0.15 and 0.25, should not exceed B factors Contributions from static and dynamic disorder Well determined ~10-20 Å 2, intermediate ~20-30 Å 2, flexible Å 2, invisible >60 Å 2. No. of observations vs. parameters Ramachandran plot

39 NMR Spectroscopy Upper limit for structure determination currently ~50 kda. Protein molecules are in solution. Dynamics, protein folding. Slow. Especially suited for studies of protein dynamics of small to medium size proteins.

40 NMR Basics NMR is nuclear magnetic resonance NMR spectroscopy is done on proteins IN SOLUTION Only atoms 1 H, 13 C, 15 N (and 31 P) can be detected in NMR experiments Proteins up to 30 kda Proteins stable at high concentration (0.5-1mM), preferably at room temperature

41 NMR Spectroscopy

42 Evalutation of NMR Structures Atomic backbone RMSD: Well-defined structures RMSDs < 0.6 Å RMSD = ( x x ) ' 2 Less well-defined structures RMSDs > 0.6 Å n 1 i n i 1T1H, Andersen et al. JBC, GF1, Cooke et al. Biochemistry, 1991

43 Evaluation of NMR Structures What regions in the structure are most well-defined? Look at the pdb ensembles to see which regions are well-defined 1RJH Nielbo et al, Biochemistry, 2003

44 Which Structural Model? Normally NMR structure models are listed according to the total energy and the number of violations. Model 1 in the PDB file is often the one with lowest energy and fewest violations. Use that model as template for modelling.

45 NMR versus X-ray Crystallography Hydrogen atoms are observed! Only 13 C, 15 N and 1 H are observed Study of proteins in solution Only proteins up to kda No total map of the structure Information used is incomplete and used as restraints An ensemble of structures is submitted to PDB The solved structure can be used for further dynamics characterization with NMR

46 PDB Holdings of the Protein Data Bank (PDB): Sep May 2006 Oct X-ray NMR Other Total The PDB also contains nucleotide and nucleotide analogue structures.

47 Summary In evolution structure is conserved longer than both function and sequence. X-ray crystallography Proteins in crystal lattice Many details one model Resolution, R-values, Ramchandran plot NMR spectroscopy Proteins in solution Fewer details many models Violations, RMSD, Ramachandran plot

48 Links PDB (protein structure database) PyMOL home: PyMOL manual: PyMOL Wiki: PyMOL settings (documented): /modules/pymol/setting.py

49 Other Courses Protein Structure and Computational Biology Master s level course 13 weeks, spring semester 5 ECTS Max. 40 students

Introduction to" Protein Structure

Introduction to Protein Structure Introduction to" Protein Structure Function, evolution & experimental methods Thomas Blicher, Center for Biological Sequence Analysis Learning Objectives Outline the basic levels of protein structure.

More information

Introduction to Comparative Protein Modeling. Chapter 4 Part I

Introduction to Comparative Protein Modeling. Chapter 4 Part I Introduction to Comparative Protein Modeling Chapter 4 Part I 1 Information on Proteins Each modeling study depends on the quality of the known experimental data. Basis of the model Search in the literature

More information

Physiochemical Properties of Residues

Physiochemical Properties of Residues Physiochemical Properties of Residues Various Sources C N Cα R Slide 1 Conformational Propensities Conformational Propensity is the frequency in which a residue adopts a given conformation (in a polypeptide)

More information

Model Mélange. Physical Models of Peptides and Proteins

Model Mélange. Physical Models of Peptides and Proteins Model Mélange Physical Models of Peptides and Proteins In the Model Mélange activity, you will visit four different stations each featuring a variety of different physical models of peptides or proteins.

More information

Protein Structures: Experiments and Modeling. Patrice Koehl

Protein Structures: Experiments and Modeling. Patrice Koehl Protein Structures: Experiments and Modeling Patrice Koehl Structural Bioinformatics: Proteins Proteins: Sources of Structure Information Proteins: Homology Modeling Proteins: Ab initio prediction Proteins:

More information

Packing of Secondary Structures

Packing of Secondary Structures 7.88 Lecture Notes - 4 7.24/7.88J/5.48J The Protein Folding and Human Disease Professor Gossard Retrieving, Viewing Protein Structures from the Protein Data Base Helix helix packing Packing of Secondary

More information

Secondary Structure. Bioch/BIMS 503 Lecture 2. Structure and Function of Proteins. Further Reading. Φ, Ψ angles alone determine protein structure

Secondary Structure. Bioch/BIMS 503 Lecture 2. Structure and Function of Proteins. Further Reading. Φ, Ψ angles alone determine protein structure Bioch/BIMS 503 Lecture 2 Structure and Function of Proteins August 28, 2008 Robert Nakamoto rkn3c@virginia.edu 2-0279 Secondary Structure Φ Ψ angles determine protein structure Φ Ψ angles are restricted

More information

Supersecondary Structures (structural motifs)

Supersecondary Structures (structural motifs) Supersecondary Structures (structural motifs) Various Sources Slide 1 Supersecondary Structures (Motifs) Supersecondary Structures (Motifs): : Combinations of secondary structures in specific geometric

More information

Basics of protein structure

Basics of protein structure Today: 1. Projects a. Requirements: i. Critical review of one paper ii. At least one computational result b. Noon, Dec. 3 rd written report and oral presentation are due; submit via email to bphys101@fas.harvard.edu

More information

Biological Macromolecules

Biological Macromolecules Introduction for Chem 493 Chemistry of Biological Macromolecules Dr. L. Luyt January 2008 Dr. L. Luyt Chem 493-2008 1 Biological macromolecules are the molecules of life allow for organization serve a

More information

Biomolecules: lecture 10

Biomolecules: lecture 10 Biomolecules: lecture 10 - understanding in detail how protein 3D structures form - realize that protein molecules are not static wire models but instead dynamic, where in principle every atom moves (yet

More information

Peptides And Proteins

Peptides And Proteins Kevin Burgess, May 3, 2017 1 Peptides And Proteins from chapter(s) in the recommended text A. Introduction B. omenclature And Conventions by amide bonds. on the left, right. 2 -terminal C-terminal triglycine

More information

Protein structure (and biomolecular structure more generally) CS/CME/BioE/Biophys/BMI 279 Sept. 28 and Oct. 3, 2017 Ron Dror

Protein structure (and biomolecular structure more generally) CS/CME/BioE/Biophys/BMI 279 Sept. 28 and Oct. 3, 2017 Ron Dror Protein structure (and biomolecular structure more generally) CS/CME/BioE/Biophys/BMI 279 Sept. 28 and Oct. 3, 2017 Ron Dror Please interrupt if you have questions, and especially if you re confused! Assignment

More information

Using Higher Calculus to Study Biologically Important Molecules Julie C. Mitchell

Using Higher Calculus to Study Biologically Important Molecules Julie C. Mitchell Using Higher Calculus to Study Biologically Important Molecules Julie C. Mitchell Mathematics and Biochemistry University of Wisconsin - Madison 0 There Are Many Kinds Of Proteins The word protein comes

More information

Exam I Answer Key: Summer 2006, Semester C

Exam I Answer Key: Summer 2006, Semester C 1. Which of the following tripeptides would migrate most rapidly towards the negative electrode if electrophoresis is carried out at ph 3.0? a. gly-gly-gly b. glu-glu-asp c. lys-glu-lys d. val-asn-lys

More information

Major Types of Association of Proteins with Cell Membranes. From Alberts et al

Major Types of Association of Proteins with Cell Membranes. From Alberts et al Major Types of Association of Proteins with Cell Membranes From Alberts et al Proteins Are Polymers of Amino Acids Peptide Bond Formation Amino Acid central carbon atom to which are attached amino group

More information

Protein structure. Protein structure. Amino acid residue. Cell communication channel. Bioinformatics Methods

Protein structure. Protein structure. Amino acid residue. Cell communication channel. Bioinformatics Methods Cell communication channel Bioinformatics Methods Iosif Vaisman Email: ivaisman@gmu.edu SEQUENCE STRUCTURE DNA Sequence Protein Sequence Protein Structure Protein structure ATGAAATTTGGAAACTTCCTTCTCACTTATCAGCCACCT...

More information

Ranjit P. Bahadur Assistant Professor Department of Biotechnology Indian Institute of Technology Kharagpur, India. 1 st November, 2013

Ranjit P. Bahadur Assistant Professor Department of Biotechnology Indian Institute of Technology Kharagpur, India. 1 st November, 2013 Hydration of protein-rna recognition sites Ranjit P. Bahadur Assistant Professor Department of Biotechnology Indian Institute of Technology Kharagpur, India 1 st November, 2013 Central Dogma of life DNA

More information

Protein Structure Bioinformatics Introduction

Protein Structure Bioinformatics Introduction 1 Swiss Institute of Bioinformatics Protein Structure Bioinformatics Introduction Basel, 27. September 2004 Torsten Schwede Biozentrum - Universität Basel Swiss Institute of Bioinformatics Klingelbergstr

More information

BIRKBECK COLLEGE (University of London)

BIRKBECK COLLEGE (University of London) BIRKBECK COLLEGE (University of London) SCHOOL OF BIOLOGICAL SCIENCES M.Sc. EXAMINATION FOR INTERNAL STUDENTS ON: Postgraduate Certificate in Principles of Protein Structure MSc Structural Molecular Biology

More information

Protein Structure. Role of (bio)informatics in drug discovery. Bioinformatics

Protein Structure. Role of (bio)informatics in drug discovery. Bioinformatics Bioinformatics Protein Structure Principles & Architecture Marjolein Thunnissen Dep. of Biochemistry & Structural Biology Lund University September 2011 Homology, pattern and 3D structure searches need

More information

Central Dogma. modifications genome transcriptome proteome

Central Dogma. modifications genome transcriptome proteome entral Dogma DA ma protein post-translational modifications genome transcriptome proteome 83 ierarchy of Protein Structure 20 Amino Acids There are 20 n possible sequences for a protein of n residues!

More information

Properties of amino acids in proteins

Properties of amino acids in proteins Properties of amino acids in proteins one of the primary roles of DNA (but not the only one!) is to code for proteins A typical bacterium builds thousands types of proteins, all from ~20 amino acids repeated

More information

Outline. Levels of Protein Structure. Primary (1 ) Structure. Lecture 6:Protein Architecture II: Secondary Structure or From peptides to proteins

Outline. Levels of Protein Structure. Primary (1 ) Structure. Lecture 6:Protein Architecture II: Secondary Structure or From peptides to proteins Lecture 6:Protein Architecture II: Secondary Structure or From peptides to proteins Margaret Daugherty Fall 2003 Outline Four levels of structure are used to describe proteins; Alpha helices and beta sheets

More information

Molecular Graphics with PyMOL

Molecular Graphics with PyMOL Molecular Graphics with PyMOL Jean)YvesSgro Instructors Molecular Graphics & Scientific Communication Ann Palmenberg Jean-Yves Sgro Marchel Hill Holly Basta H. Adam Steinberg 1 Lab Book : Section 1 Computer

More information

Structure and evolution of the spliceosomal peptidyl-prolyl cistrans isomerase Cwc27

Structure and evolution of the spliceosomal peptidyl-prolyl cistrans isomerase Cwc27 Acta Cryst. (2014). D70, doi:10.1107/s1399004714021695 Supporting information Volume 70 (2014) Supporting information for article: Structure and evolution of the spliceosomal peptidyl-prolyl cistrans isomerase

More information

Protein Structure Marianne Øksnes Dalheim, PhD candidate Biopolymers, TBT4135, Autumn 2013

Protein Structure Marianne Øksnes Dalheim, PhD candidate Biopolymers, TBT4135, Autumn 2013 Protein Structure Marianne Øksnes Dalheim, PhD candidate Biopolymers, TBT4135, Autumn 2013 The presentation is based on the presentation by Professor Alexander Dikiy, which is given in the course compedium:

More information

Protein Structure Basics

Protein Structure Basics Protein Structure Basics Presented by Alison Fraser, Christine Lee, Pradhuman Jhala, Corban Rivera Importance of Proteins Muscle structure depends on protein-protein interactions Transport across membranes

More information

Giri Narasimhan. CAP 5510: Introduction to Bioinformatics. ECS 254; Phone: x3748

Giri Narasimhan. CAP 5510: Introduction to Bioinformatics. ECS 254; Phone: x3748 CAP 5510: Introduction to Bioinformatics Giri Narasimhan ECS 254; Phone: x3748 giri@cis.fiu.edu www.cis.fiu.edu/~giri/teach/bioinfs07.html 2/15/07 CAP5510 1 EM Algorithm Goal: Find θ, Z that maximize Pr

More information

1. What is an ångstrom unit, and why is it used to describe molecular structures?

1. What is an ångstrom unit, and why is it used to describe molecular structures? 1. What is an ångstrom unit, and why is it used to describe molecular structures? The ångstrom unit is a unit of distance suitable for measuring atomic scale objects. 1 ångstrom (Å) = 1 10-10 m. The diameter

More information

Section Week 3. Junaid Malek, M.D.

Section Week 3. Junaid Malek, M.D. Section Week 3 Junaid Malek, M.D. Biological Polymers DA 4 monomers (building blocks), limited structure (double-helix) RA 4 monomers, greater flexibility, multiple structures Proteins 20 Amino Acids,

More information

Biochemistry Quiz Review 1I. 1. Of the 20 standard amino acids, only is not optically active. The reason is that its side chain.

Biochemistry Quiz Review 1I. 1. Of the 20 standard amino acids, only is not optically active. The reason is that its side chain. Biochemistry Quiz Review 1I A general note: Short answer questions are just that, short. Writing a paragraph filled with every term you can remember from class won t improve your answer just answer clearly,

More information

Read more about Pauling and more scientists at: Profiles in Science, The National Library of Medicine, profiles.nlm.nih.gov

Read more about Pauling and more scientists at: Profiles in Science, The National Library of Medicine, profiles.nlm.nih.gov 2018 Biochemistry 110 California Institute of Technology Lecture 2: Principles of Protein Structure Linus Pauling (1901-1994) began his studies at Caltech in 1922 and was directed by Arthur Amos oyes to

More information

From Amino Acids to Proteins - in 4 Easy Steps

From Amino Acids to Proteins - in 4 Easy Steps From Amino Acids to Proteins - in 4 Easy Steps Although protein structure appears to be overwhelmingly complex, you can provide your students with a basic understanding of how proteins fold by focusing

More information

NMR study of complexes between low molecular mass inhibitors and the West Nile virus NS2B-NS3 protease

NMR study of complexes between low molecular mass inhibitors and the West Nile virus NS2B-NS3 protease University of Wollongong Research Online Faculty of Science - Papers (Archive) Faculty of Science, Medicine and Health 2009 NMR study of complexes between low molecular mass inhibitors and the West Nile

More information

Introduction to the Ribosome Overview of protein synthesis on the ribosome Prof. Anders Liljas

Introduction to the Ribosome Overview of protein synthesis on the ribosome Prof. Anders Liljas Introduction to the Ribosome Molecular Biophysics Lund University 1 A B C D E F G H I J Genome Protein aa1 aa2 aa3 aa4 aa5 aa6 aa7 aa10 aa9 aa8 aa11 aa12 aa13 a a 14 How is a polypeptide synthesized? 2

More information

Viewing and Analyzing Proteins, Ligands and their Complexes 2

Viewing and Analyzing Proteins, Ligands and their Complexes 2 2 Viewing and Analyzing Proteins, Ligands and their Complexes 2 Overview Viewing the accessible surface Analyzing the properties of proteins containing thousands of atoms is best accomplished by representing

More information

Lecture 10 (10/4/17) Lecture 10 (10/4/17)

Lecture 10 (10/4/17) Lecture 10 (10/4/17) Lecture 10 (10/4/17) Reading: Ch4; 125, 138-141, 141-142 Problems: Ch4 (text); 7, 9, 11 Ch4 (study guide); 1, 2 NEXT Reading: Ch4; 125, 132-136 (structure determination) Ch4; 12-130 (Collagen) Problems:

More information

Sequential resonance assignments in (small) proteins: homonuclear method 2º structure determination

Sequential resonance assignments in (small) proteins: homonuclear method 2º structure determination Lecture 9 M230 Feigon Sequential resonance assignments in (small) proteins: homonuclear method 2º structure determination Reading resources v Roberts NMR of Macromolecules, Chap 4 by Christina Redfield

More information

What makes a good graphene-binding peptide? Adsorption of amino acids and peptides at aqueous graphene interfaces: Electronic Supplementary

What makes a good graphene-binding peptide? Adsorption of amino acids and peptides at aqueous graphene interfaces: Electronic Supplementary Electronic Supplementary Material (ESI) for Journal of Materials Chemistry B. This journal is The Royal Society of Chemistry 21 What makes a good graphene-binding peptide? Adsorption of amino acids and

More information

Computer simulations of protein folding with a small number of distance restraints

Computer simulations of protein folding with a small number of distance restraints Vol. 49 No. 3/2002 683 692 QUARTERLY Computer simulations of protein folding with a small number of distance restraints Andrzej Sikorski 1, Andrzej Kolinski 1,2 and Jeffrey Skolnick 2 1 Department of Chemistry,

More information

Protein Dynamics. The space-filling structures of myoglobin and hemoglobin show that there are no pathways for O 2 to reach the heme iron.

Protein Dynamics. The space-filling structures of myoglobin and hemoglobin show that there are no pathways for O 2 to reach the heme iron. Protein Dynamics The space-filling structures of myoglobin and hemoglobin show that there are no pathways for O 2 to reach the heme iron. Below is myoglobin hydrated with 350 water molecules. Only a small

More information

Summary of Experimental Protein Structure Determination. Key Elements

Summary of Experimental Protein Structure Determination. Key Elements Programme 8.00-8.20 Summary of last week s lecture and quiz 8.20-9.00 Structure validation 9.00-9.15 Break 9.15-11.00 Exercise: Structure validation tutorial 11.00-11.10 Break 11.10-11.40 Summary & discussion

More information

Final Chem 4511/6501 Spring 2011 May 5, 2011 b Name

Final Chem 4511/6501 Spring 2011 May 5, 2011 b Name Key 1) [10 points] In RNA, G commonly forms a wobble pair with U. a) Draw a G-U wobble base pair, include riboses and 5 phosphates. b) Label the major groove and the minor groove. c) Label the atoms of

More information

Protein Struktur (optional, flexible)

Protein Struktur (optional, flexible) Protein Struktur (optional, flexible) 22/10/2009 [ 1 ] Andrew Torda, Wintersemester 2009 / 2010, AST nur für Informatiker, Mathematiker,.. 26 kt, 3 ov 2009 Proteins - who cares? 22/10/2009 [ 2 ] Most important

More information

Lecture 2 and 3: Review of forces (ctd.) and elementary statistical mechanics. Contributions to protein stability

Lecture 2 and 3: Review of forces (ctd.) and elementary statistical mechanics. Contributions to protein stability Lecture 2 and 3: Review of forces (ctd.) and elementary statistical mechanics. Contributions to protein stability Part I. Review of forces Covalent bonds Non-covalent Interactions: Van der Waals Interactions

More information

Analysis and Prediction of Protein Structure (I)

Analysis and Prediction of Protein Structure (I) Analysis and Prediction of Protein Structure (I) Jianlin Cheng, PhD School of Electrical Engineering and Computer Science University of Central Florida 2006 Free for academic use. Copyright @ Jianlin Cheng

More information

Supplementary Figure 3 a. Structural comparison between the two determined structures for the IL 23:MA12 complex. The overall RMSD between the two

Supplementary Figure 3 a. Structural comparison between the two determined structures for the IL 23:MA12 complex. The overall RMSD between the two Supplementary Figure 1. Biopanningg and clone enrichment of Alphabody binders against human IL 23. Positive clones in i phage ELISA with optical density (OD) 3 times higher than background are shown for

More information

THE UNIVERSITY OF MANITOBA. PAPER NO: 409 LOCATION: Fr. Kennedy Gold Gym PAGE NO: 1 of 6 DEPARTMENT & COURSE NO: CHEM 4630 TIME: 3 HOURS

THE UNIVERSITY OF MANITOBA. PAPER NO: 409 LOCATION: Fr. Kennedy Gold Gym PAGE NO: 1 of 6 DEPARTMENT & COURSE NO: CHEM 4630 TIME: 3 HOURS PAPER NO: 409 LOCATION: Fr. Kennedy Gold Gym PAGE NO: 1 of 6 DEPARTMENT & COURSE NO: CHEM 4630 TIME: 3 HOURS EXAMINATION: Biochemistry of Proteins EXAMINER: J. O'Neil Section 1: You must answer all of

More information

F. Piazza Center for Molecular Biophysics and University of Orléans, France. Selected topic in Physical Biology. Lecture 1

F. Piazza Center for Molecular Biophysics and University of Orléans, France. Selected topic in Physical Biology. Lecture 1 Zhou Pei-Yuan Centre for Applied Mathematics, Tsinghua University November 2013 F. Piazza Center for Molecular Biophysics and University of Orléans, France Selected topic in Physical Biology Lecture 1

More information

Basic structures of proteins

Basic structures of proteins Basic structures of proteins Structural Hierarchy of Protein Primary structure Functional elements : α-helix, strands, β-sheet, loops.. - Structure, affinity, activity, specificity, stability etc. Secondary

More information

Supplementary figure 1. Comparison of unbound ogm-csf and ogm-csf as captured in the GIF:GM-CSF complex. Alignment of two copies of unbound ovine

Supplementary figure 1. Comparison of unbound ogm-csf and ogm-csf as captured in the GIF:GM-CSF complex. Alignment of two copies of unbound ovine Supplementary figure 1. Comparison of unbound and as captured in the GIF:GM-CSF complex. Alignment of two copies of unbound ovine GM-CSF (slate) with bound GM-CSF in the GIF:GM-CSF complex (GIF: green,

More information

Objective: Students will be able identify peptide bonds in proteins and describe the overall reaction between amino acids that create peptide bonds.

Objective: Students will be able identify peptide bonds in proteins and describe the overall reaction between amino acids that create peptide bonds. Scott Seiple AP Biology Lesson Plan Lesson: Primary and Secondary Structure of Proteins Purpose:. To understand how amino acids can react to form peptides through peptide bonds.. Students will be able

More information

Programme Last week s quiz results + Summary Fold recognition Break Exercise: Modelling remote homologues

Programme Last week s quiz results + Summary Fold recognition Break Exercise: Modelling remote homologues Programme 8.00-8.20 Last week s quiz results + Summary 8.20-9.00 Fold recognition 9.00-9.15 Break 9.15-11.20 Exercise: Modelling remote homologues 11.20-11.40 Summary & discussion 11.40-12.00 Quiz 1 Feedback

More information

Advanced Certificate in Principles in Protein Structure. You will be given a start time with your exam instructions

Advanced Certificate in Principles in Protein Structure. You will be given a start time with your exam instructions BIRKBECK COLLEGE (University of London) Advanced Certificate in Principles in Protein Structure MSc Structural Molecular Biology Date: Thursday, 1st September 2011 Time: 3 hours You will be given a start

More information

Outline. Levels of Protein Structure. Primary (1 ) Structure. Lecture 6:Protein Architecture II: Secondary Structure or From peptides to proteins

Outline. Levels of Protein Structure. Primary (1 ) Structure. Lecture 6:Protein Architecture II: Secondary Structure or From peptides to proteins Lecture 6:Protein Architecture II: Secondary Structure or From peptides to proteins Margaret Daugherty Fall 2004 Outline Four levels of structure are used to describe proteins; Alpha helices and beta sheets

More information

CAP 5510 Lecture 3 Protein Structures

CAP 5510 Lecture 3 Protein Structures CAP 5510 Lecture 3 Protein Structures Su-Shing Chen Bioinformatics CISE 8/19/2005 Su-Shing Chen, CISE 1 Protein Conformation 8/19/2005 Su-Shing Chen, CISE 2 Protein Conformational Structures Hydrophobicity

More information

Chemistry Chapter 22

Chemistry Chapter 22 hemistry 2100 hapter 22 Proteins Proteins serve many functions, including the following. 1. Structure: ollagen and keratin are the chief constituents of skin, bone, hair, and nails. 2. atalysts: Virtually

More information

BCH 4053 Exam I Review Spring 2017

BCH 4053 Exam I Review Spring 2017 BCH 4053 SI - Spring 2017 Reed BCH 4053 Exam I Review Spring 2017 Chapter 1 1. Calculate G for the reaction A + A P + Q. Assume the following equilibrium concentrations: [A] = 20mM, [Q] = [P] = 40fM. Assume

More information

Computer design of idealized -motifs

Computer design of idealized -motifs Computer design of idealized -motifs Andrzej Kolinski a) University of Warsaw, Department of Chemistry, Pasteura 1, 02-093 Warsaw, Poland and The Scripps Research Institute, Department of Molecular Biology,

More information

ALL LECTURES IN SB Introduction

ALL LECTURES IN SB Introduction 1. Introduction 2. Molecular Architecture I 3. Molecular Architecture II 4. Molecular Simulation I 5. Molecular Simulation II 6. Bioinformatics I 7. Bioinformatics II 8. Prediction I 9. Prediction II ALL

More information

HIV protease inhibitor. Certain level of function can be found without structure. But a structure is a key to understand the detailed mechanism.

HIV protease inhibitor. Certain level of function can be found without structure. But a structure is a key to understand the detailed mechanism. Proteins are linear polypeptide chains (one or more) Building blocks: 20 types of amino acids. Range from a few 10s-1000s They fold into varying three-dimensional shapes structure medicine Certain level

More information

A) at equilibrium B) endergonic C) endothermic D) exergonic E) exothermic.

A) at equilibrium B) endergonic C) endothermic D) exergonic E) exothermic. CHEM 2770: Elements of Biochemistry Mid Term EXAMINATION VERSION A Date: October 29, 2014 Instructor: H. Perreault Location: 172 Schultz Time: 4 or 6 pm. Duration: 1 hour Instructions Please mark the Answer

More information

Figure 1. Molecules geometries of 5021 and Each neutral group in CHARMM topology was grouped in dash circle.

Figure 1. Molecules geometries of 5021 and Each neutral group in CHARMM topology was grouped in dash circle. Project I Chemistry 8021, Spring 2005/2/23 This document was turned in by a student as a homework paper. 1. Methods First, the cartesian coordinates of 5021 and 8021 molecules (Fig. 1) are generated, in

More information

THE UNIVERSITY OF MANITOBA. PAPER NO: _1_ LOCATION: 173 Robert Schultz Theatre PAGE NO: 1 of 5 DEPARTMENT & COURSE NO: CHEM / MBIO 2770 TIME: 1 HOUR

THE UNIVERSITY OF MANITOBA. PAPER NO: _1_ LOCATION: 173 Robert Schultz Theatre PAGE NO: 1 of 5 DEPARTMENT & COURSE NO: CHEM / MBIO 2770 TIME: 1 HOUR THE UNIVERSITY OF MANITOBA 1 November 1, 2016 Mid-Term EXAMINATION PAPER NO: _1_ LOCATION: 173 Robert Schultz Theatre PAGE NO: 1 of 5 DEPARTMENT & COURSE NO: CHEM / MBIO 2770 TIME: 1 HOUR EXAMINATION:

More information

Protein Structure. W. M. Grogan, Ph.D. OBJECTIVES

Protein Structure. W. M. Grogan, Ph.D. OBJECTIVES Protein Structure W. M. Grogan, Ph.D. OBJECTIVES 1. Describe the structure and characteristic properties of typical proteins. 2. List and describe the four levels of structure found in proteins. 3. Relate

More information

Announcements. Primary (1 ) Structure. Lecture 7 & 8: PROTEIN ARCHITECTURE IV: Tertiary and Quaternary Structure

Announcements. Primary (1 ) Structure. Lecture 7 & 8: PROTEIN ARCHITECTURE IV: Tertiary and Quaternary Structure Announcements TA Office Hours: Brian Eckenroth Monday 3-4 pm Thursday 11 am-12 pm Lecture 7 & 8: PROTEIN ARCHITECTURE IV: Tertiary and Quaternary Structure Margaret Daugherty Fall 2003 Homework II posted

More information

BSc and MSc Degree Examinations

BSc and MSc Degree Examinations Examination Candidate Number: Desk Number: BSc and MSc Degree Examinations 2018-9 Department : BIOLOGY Title of Exam: Molecular Biology and Biochemistry Part I Time Allowed: 1 hour and 30 minutes Marking

More information

Problem Set 1

Problem Set 1 2006 7.012 Problem Set 1 Due before 5 PM on FRIDAY, September 15, 2006. Turn answers in to the box outside of 68-120. PLEASE WRITE YOUR ANSWERS ON THIS PRINTOUT. 1. For each of the following parts, pick

More information

D Dobbs ISU - BCB 444/544X 1

D Dobbs ISU - BCB 444/544X 1 11/7/05 Protein Structure: Classification, Databases, Visualization Announcements BCB 544 Projects - Important Dates: Nov 2 Wed noon - Project proposals due to David/Drena Nov 4 Fri PM - Approvals/responses

More information

4 Proteins: Structure, Function, Folding W. H. Freeman and Company

4 Proteins: Structure, Function, Folding W. H. Freeman and Company 4 Proteins: Structure, Function, Folding 2013 W. H. Freeman and Company CHAPTER 4 Proteins: Structure, Function, Folding Learning goals: Structure and properties of the peptide bond Structural hierarchy

More information

Protein Data Bank Contents Guide: Atomic Coordinate Entry Format Description. Version Document Published by the wwpdb

Protein Data Bank Contents Guide: Atomic Coordinate Entry Format Description. Version Document Published by the wwpdb Protein Data Bank Contents Guide: Atomic Coordinate Entry Format Description Version 3.30 Document Published by the wwpdb This format complies with the PDB Exchange Dictionary (PDBx) http://mmcif.pdb.org/dictionaries/mmcif_pdbx.dic/index/index.html.

More information

B O C 4 H 2 O O. NOTE: The reaction proceeds with a carbonium ion stabilized on the C 1 of sugar A.

B O C 4 H 2 O O. NOTE: The reaction proceeds with a carbonium ion stabilized on the C 1 of sugar A. hbcse 33 rd International Page 101 hemistry lympiad Preparatory 05/02/01 Problems d. In the hydrolysis of the glycosidic bond, the glycosidic bridge oxygen goes with 4 of the sugar B. n cleavage, 18 from

More information

April, The energy functions include:

April, The energy functions include: REDUX A collection of Python scripts for torsion angle Monte Carlo protein molecular simulations and analysis The program is based on unified residue peptide model and is designed for more efficient exploration

More information

Basic Principles of Protein Structures

Basic Principles of Protein Structures Basic Principles of Protein Structures Proteins Proteins: The Molecule of Life Proteins: Building Blocks Proteins: Secondary Structures Proteins: Tertiary and Quartenary Structure Proteins: Geometry Proteins

More information

Translation. A ribosome, mrna, and trna.

Translation. A ribosome, mrna, and trna. Translation The basic processes of translation are conserved among prokaryotes and eukaryotes. Prokaryotic Translation A ribosome, mrna, and trna. In the initiation of translation in prokaryotes, the Shine-Dalgarno

More information

HSQC spectra for three proteins

HSQC spectra for three proteins HSQC spectra for three proteins SH3 domain from Abp1p Kinase domain from EphB2 apo Calmodulin What do the spectra tell you about the three proteins? HSQC spectra for three proteins Small protein Big protein

More information

PROTEIN SECONDARY STRUCTURE PREDICTION: AN APPLICATION OF CHOU-FASMAN ALGORITHM IN A HYPOTHETICAL PROTEIN OF SARS VIRUS

PROTEIN SECONDARY STRUCTURE PREDICTION: AN APPLICATION OF CHOU-FASMAN ALGORITHM IN A HYPOTHETICAL PROTEIN OF SARS VIRUS Int. J. LifeSc. Bt & Pharm. Res. 2012 Kaladhar, 2012 Research Paper ISSN 2250-3137 www.ijlbpr.com Vol.1, Issue. 1, January 2012 2012 IJLBPR. All Rights Reserved PROTEIN SECONDARY STRUCTURE PREDICTION:

More information

Exam III. Please read through each question carefully, and make sure you provide all of the requested information.

Exam III. Please read through each question carefully, and make sure you provide all of the requested information. 09-107 onors Chemistry ame Exam III Please read through each question carefully, and make sure you provide all of the requested information. 1. A series of octahedral metal compounds are made from 1 mol

More information

Chapter 4: Amino Acids

Chapter 4: Amino Acids Chapter 4: Amino Acids All peptides and polypeptides are polymers of alpha-amino acids. lipid polysaccharide enzyme 1940s 1980s. Lipids membrane 1960s. Polysaccharide Are energy metabolites and many of

More information

Supporting information to: Time-resolved observation of protein allosteric communication. Sebastian Buchenberg, Florian Sittel and Gerhard Stock 1

Supporting information to: Time-resolved observation of protein allosteric communication. Sebastian Buchenberg, Florian Sittel and Gerhard Stock 1 Supporting information to: Time-resolved observation of protein allosteric communication Sebastian Buchenberg, Florian Sittel and Gerhard Stock Biomolecular Dynamics, Institute of Physics, Albert Ludwigs

More information

Proteins: Characteristics and Properties of Amino Acids

Proteins: Characteristics and Properties of Amino Acids SBI4U:Biochemistry Macromolecules Eachaminoacidhasatleastoneamineandoneacidfunctionalgroupasthe nameimplies.thedifferentpropertiesresultfromvariationsinthestructuresof differentrgroups.thergroupisoftenreferredtoastheaminoacidsidechain.

More information

Principles of Physical Biochemistry

Principles of Physical Biochemistry Principles of Physical Biochemistry Kensal E. van Hold e W. Curtis Johnso n P. Shing Ho Preface x i PART 1 MACROMOLECULAR STRUCTURE AND DYNAMICS 1 1 Biological Macromolecules 2 1.1 General Principles

More information

UNIT TWELVE. a, I _,o "' I I I. I I.P. l'o. H-c-c. I ~o I ~ I / H HI oh H...- I II I II 'oh. HO\HO~ I "-oh

UNIT TWELVE. a, I _,o ' I I I. I I.P. l'o. H-c-c. I ~o I ~ I / H HI oh H...- I II I II 'oh. HO\HO~ I -oh UNT TWELVE PROTENS : PEPTDE BONDNG AND POLYPEPTDES 12 CONCEPTS Many proteins are important in biological structure-for example, the keratin of hair, collagen of skin and leather, and fibroin of silk. Other

More information

Protein Struktur. Biologen und Chemiker dürfen mit Handys spielen (leise) go home, go to sleep. wake up at slide 39

Protein Struktur. Biologen und Chemiker dürfen mit Handys spielen (leise) go home, go to sleep. wake up at slide 39 Protein Struktur Biologen und Chemiker dürfen mit Handys spielen (leise) go home, go to sleep wake up at slide 39 Andrew Torda, Wintersemester 2016/ 2017 Andrew Torda 17.10.2016 [ 1 ] Proteins - who cares?

More information

The Structure of Enzymes!

The Structure of Enzymes! The Structure of Enzymes Levels of Protein Structure 0 order amino acid composition Primary Secondary Motifs Tertiary Domains Quaternary ther sequence repeating structural patterns defined by torsion angles

More information

The Structure of Enzymes!

The Structure of Enzymes! The Structure of Enzymes Levels of Protein Structure 0 order amino acid composition Primary Secondary Motifs Tertiary Domains Quaternary ther sequence repeating structural patterns defined by torsion angles

More information

Biotechnology of Proteins. The Source of Stability in Proteins (III) Fall 2015

Biotechnology of Proteins. The Source of Stability in Proteins (III) Fall 2015 Biotechnology of Proteins The Source of Stability in Proteins (III) Fall 2015 Conformational Entropy of Unfolding It is The factor that makes the greatest contribution to stabilization of the unfolded

More information

THE TANGO ALGORITHM: SECONDARY STRUCTURE PROPENSITIES, STATISTICAL MECHANICS APPROXIMATION

THE TANGO ALGORITHM: SECONDARY STRUCTURE PROPENSITIES, STATISTICAL MECHANICS APPROXIMATION THE TANGO ALGORITHM: SECONDARY STRUCTURE PROPENSITIES, STATISTICAL MECHANICS APPROXIMATION AND CALIBRATION Calculation of turn and beta intrinsic propensities. A statistical analysis of a protein structure

More information

Protein Structures. Sequences of amino acid residues 20 different amino acids. Quaternary. Primary. Tertiary. Secondary. 10/8/2002 Lecture 12 1

Protein Structures. Sequences of amino acid residues 20 different amino acids. Quaternary. Primary. Tertiary. Secondary. 10/8/2002 Lecture 12 1 Protein Structures Sequences of amino acid residues 20 different amino acids Primary Secondary Tertiary Quaternary 10/8/2002 Lecture 12 1 Angles φ and ψ in the polypeptide chain 10/8/2002 Lecture 12 2

More information

Biochemistry: Concepts and Connections

Biochemistry: Concepts and Connections Biochemistry: Concepts and Connections Dean R. Appling Spencer J. Anthony-Cahill Christopher K. Mathews Chapter 6 The Three Dimensional Structure of Proteins Cartoon representation of myoglobin, showing

More information

Any protein that can be labelled by both procedures must be a transmembrane protein.

Any protein that can be labelled by both procedures must be a transmembrane protein. 1. What kind of experimental evidence would indicate that a protein crosses from one side of the membrane to the other? Regions of polypeptide part exposed on the outside of the membrane can be probed

More information

Biochemistry Prof. S. DasGupta Department of Chemistry Indian Institute of Technology Kharagpur. Lecture - 06 Protein Structure IV

Biochemistry Prof. S. DasGupta Department of Chemistry Indian Institute of Technology Kharagpur. Lecture - 06 Protein Structure IV Biochemistry Prof. S. DasGupta Department of Chemistry Indian Institute of Technology Kharagpur Lecture - 06 Protein Structure IV We complete our discussion on Protein Structures today. And just to recap

More information

BCH 4053 Spring 2003 Chapter 6 Lecture Notes

BCH 4053 Spring 2003 Chapter 6 Lecture Notes BCH 4053 Spring 2003 Chapter 6 Lecture Notes 1 CHAPTER 6 Proteins: Secondary, Tertiary, and Quaternary Structure 2 Levels of Protein Structure Primary (sequence) Secondary (ordered structure along peptide

More information

The Structure and Functions of Proteins

The Structure and Functions of Proteins Wright State University CORE Scholar Computer Science and Engineering Faculty Publications Computer Science and Engineering 2003 The Structure and Functions of Proteins Dan E. Krane Wright State University

More information

The protein folding problem consists of two parts:

The protein folding problem consists of two parts: Energetics and kinetics of protein folding The protein folding problem consists of two parts: 1)Creating a stable, well-defined structure that is significantly more stable than all other possible structures.

More information

Copyright Mark Brandt, Ph.D A third method, cryogenic electron microscopy has seen increasing use over the past few years.

Copyright Mark Brandt, Ph.D A third method, cryogenic electron microscopy has seen increasing use over the past few years. Structure Determination and Sequence Analysis The vast majority of the experimentally determined three-dimensional protein structures have been solved by one of two methods: X-ray diffraction and Nuclear

More information

Computational Protein Design

Computational Protein Design 11 Computational Protein Design This chapter introduces the automated protein design and experimental validation of a novel designed sequence, as described in Dahiyat and Mayo [1]. 11.1 Introduction Given

More information

BBS501 Section 1 9:00 am 10:00 am Monday thru Friday LRC 105 A & B

BBS501 Section 1 9:00 am 10:00 am Monday thru Friday LRC 105 A & B BBS501 Section 1 9:00 am 10:00 am Monday thru Friday LRC 105 A & B Lecturers: Dr. Yie-Hwa Chang Room M130 Phone: #79263 E-mail:changy@slu.edu Dr. Tomasz Heyduk Room M99 Phone: #79238 E-mail: heydukt@slu.edu

More information

Secondary and sidechain structures

Secondary and sidechain structures Lecture 2 Secondary and sidechain structures James Chou BCMP201 Spring 2008 Images from Petsko & Ringe, Protein Structure and Function. Branden & Tooze, Introduction to Protein Structure. Richardson, J.

More information