Assignments 2019

Fall 2019

Assignment Pages for Fall 2019 Struct and Phys Biochem
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Foundations Sept 4th

Reading (to be completed before class!)   

Lehninger
Chp 1: 1.1, Cellular Foundations, 1.2 Chemical Foundations, 1.3 Physical Foundations

Background knowledge: Chirality and Stereochemistry; Functional Groups; Thermodynamics; Coupled Reactions

Terms and Figures to know and understand:
Sect 1.1: Bold terms, Fig 1-11
Sect 1.2: Fig 1-17, Bold terms for configuration and confirmation, Figs 1-21, -22, -23, -24, -25, R-S.
Sect 1.3: Bold terms, equations, Fig 1-29

Example Pre-Assignment: Bring notes taken while reading text and 1 question from the reading to class

In Class Activities

Discussion of Syllabus
Worksheet: Chirality and Stereochemistry; Functional Groups; Thermodynamics; Coupled Reactions (slide show)
Worksheet key

Problems

Lehninger
Chp 1: 7, 8, 11, 12, 14, 15

 


Water - Sept 6th

Reading (to be completed before class!)   

Lehninger
Chp 2: 2.2-2.4 Acid-base, buffers (we will cover 2.1 in the next lecture)
 
Terms and Figures to know and understand:
Sect 2.2 bold terms, equations 2-3, 2-4, 2-7, 2-8, 2-9, Figs 2-16, 2-18, 2-19, 2-21
 
Pre-Assignment

In Class Activities

Worksheet: Acid-base biochemistry  key

Problems

Lehninger
Chp 2: 1, 2, 3, 7, 10, 11, 13, 14a,b, 15, 16, 17, 20, 22, 24, 27, 28, 31, 35

 


Aqueous Solutions Sept 9th

Reading (to be completed before class!)   

Lehninger
Chp 2: 2.1 Aqueous solutions, weak interactions

Terms and Figures to know and understand:
all terms in bold through page 54, acceptor and donor, Fig 2-3, 2-4, Proporties and IFs Fig2-5, 2-6, Fig2-8 (very important), equation F =Q1Q2/εr2, colligative properties, Fig2-13

Article
NATURE | VOL 430 | 1 JULY 2004.
Context-dependent contributions of backbone hydrogen bonding to β-sheet folding energetics.
READ abstract and text related to figures 1 and 2.
 
Pre_Class Assignment: Bring notes from the assigned reading and two questions from the reading to class

In Class Activities

Worksheet: Properties of water        Key

Problems

Lehninger
Chp 2: 1*, 2*, 3*, 7, 10, 11, 13, 14a,b, 15, 16, 17, 20, 22, 24, 27, 28, 31, 35


 

Primary Structure with Intro to Molecular Modeling Sept 11th

Reading (to be completed before class!)

Lehninger
  • Chp 3: 3.1, 3.2, 3.4 Amino Acids, Primary Structure
  • Chp 3: 3.3 (discussed in lab)

Terms and Figures to know and understand:

  • Section 3.1: Bold terms (except uncommon amino acids), Fig 3-2 and 3-5, Assign stereoisomersim (Fig 3-3), Box 3-1 and Fig 3-6 (know amino acids that absorb light and Beer's Law), pI,
  • Section 3.2: Know terms in bold, Fig 3-13, Fig 3-14, be able to draw the formation of a peptide bond. You do not have to memorize specific phi and psi angles, Fig 3-7 (formation of disulfide bonds)

Pre-Assignment

  1. PreAssignment Worksheet: Amino acids and the primary and secondary structure of proteins
  2. Download Deepview (SwissPDB viewer) to your computer.
    Read The Intro to the Deepview turorial and do parts 1 (Getting Started) and 2 (Windows)

In Class Activities

  1. Short lecture/discussion

Upcoming Assignments

  • Molecular Modeling wih Swiss PdbViewer 
    Tutorials 3-8  Please complete by Mon the 18th before class
  • Deepview Assignment 1 - Views 1-8, DS-1 (view 9 with caption)
    Due Fri the 20th end of day (pleases send all files via email or share with me in a Google folder)

 


Amino Acids (see table 3-1 and Fig 3-5)

  • Memorize Names and 3 and 1 Letter Abbreviations
  • Know Categories to which each AA belongs (nonpolar, neutral polar charged, etc)
  • Be able to match structure of the AA to its name
  • Know approximate pKas for backbone amines and carboxylic acids, charged side chains

Problems: Lehninger
Chapter 3: 1, 2, 3a, 4b,c, 6, 7, 11
Chapter 4: 1
Chp 3 (Methods Problems): 5, 10, 15*, 17
(Methods problems are assigned to support lab. These are review problems and not covered in class. Please see me ASAP if you need assistance)


 

Primary and Secondary Structure (cont) - Sept 13th

Reading
Lehninger 7th ed
Chapter 4: Sections 1-3, pages 115-142

Suggested Reading
Berg Biochemistry Chp 3: 3.2 (May help with torsion angles,
cis and trans peptide bonds, and the Ramachandran plot.)

Terms and Figures to know and understand:

Section 4.1-4.2: Bold terms, phi and psi (fig 4-2, 4-3,and 4-9)

Pre-Assignment

Short lecture/discussion

Problems

  • Lehninger 7th ed
    Chapter 4: 1, 4, 6, 7, 10, 13, 16

Upcoming Assignments

  • Molecular Modeling wih Swiss PdbViewer 
    Tutorials 1-8  Please complete by Wed the 18th before class
  • Deepview Assignment 1 - Views 1-8, DS-1 (view 9 with caption)
    Due Fri the 20th end of day (pleases send all files via email or share with me in a Google folder)

Intro to Molecular Modeling and Sec and Tert Structure - Sept 16th

Reading (to be completed before class!)

Review Chp 4.1-4.3

Outcomes

  • Molecular modeling
  • Identify seconday structure types
  • Understand the role of Phi and Psi in limiting conformational freedom in proteins
  • Identify and study secondary structure using molecular modeling software
  • Be able to use a Ramachandran plot to study secondary structure

Review Pre-Assignments


In Class Activities

Problems

  •  Deepview Assignment 1 - Views 1-8, DS-1 (view 9 with caption)
    • Due Fri the 20th end of day (pleases send all files via email or share with me in a Google folder)

 

3D Structure of Proteins - Sept 18th

Reading (to be completed before class!)

Lehninger 7th ed
Chp 4: 4.3
 
Supplemental Reading
  • Berg Biochemistry
    Chp3: 3.3, 3.4, 3.5 Protein3D Structure

Outcomes:

  1. Know or identify
      • Tertiary and quaternary structure
      • Motif
      • Domain
      • Protein family
      • Disulfide bond
      • Subunit
  2. Identify stabilizing factors in tertiary and quaternary structure
  3. Use Swiss PDB viewer to exam a a-helix
  4. Use Swiss-Pdb Viewer to examine intermolecular interfaces between subunits.

Know from Reading:

  • Fundemental difference between Fibrous proteins and Globular proteins
  • Terms in Bold starting at Structural Diversity Reflects Functional Diversity (p130)
  • Fig 4-18 (motifs), 4-19 (domains), 4-23 (folding patterns)

In Class Activities

3D Structure of Proteins Worksheet

Quaternary Structure Worksheet (essentially tutorial 10 in Deepview)

Problems

  • Lehninger: 7, 9, 13
  • Berg Chp 3 (5th ed): 2, 3, 6, 7, 9
  • Voet: Chp8: 2, 4 (also using Swiss PDBviewer), 18 (also support your answer using SwissPDBviewer), 22  Solutions

- Molecular Modeling wih Swiss PdbViewer
Tutorials 7, 10 , 11 (Try tutorial 10 with 1 HHO.pdb , READ Note!)


 

Thermodynamics and Macromolecules - Sept 23rd

Reading (to be completed before class!)

  • Lehninger does not do justice to this topic. Here is what they have. I have added some what I consider better options for reading

    • Lehninger Chp 1. Sect 1.3
    • Lehninger Chp 4. Sect 4.1. p116-117
  • *Whitford - Proteins: Structure and Function: Interactions Stabilizing Proteins: pages 53-58
    (This is the best prepartion for the worksheet)

Suggested

  • Very Helpful Review
    Voet 4th ed
    Chp 3: all
    Chp 8, Sect 4

In Class Activities

  • BRING your text or have online reference available in CLASS
  • Complete Group Problem
    • Also on Workseet on Intermolecular forces, thermodynamics, and protein stability
  • ON HEAT CAPACITY and HYDROPHOBIC EFFECT
    Focus on first two pages
    PNAS June 1, 1977 vol. 74 no. 6 2236-2240

Problems

There are no problems on this topic available in Lehninger.

Additional Problems: Worksheet

Thermodynamics and Folding    key

Interpret the table below to answer the following questions (adapted from Fiore et al. Biochem. 2009, 48, 2550): Thermodynamic parameters for folding of structured RNAs

  • Is the folding of these RNA molecules driven by the same forces as the peptides discussed in class? Justify your answer.
  • Calculate the ΔGo for each RNA (assume 298K). Is folding spontaneous?
     RNA  ΔHo (kcal/mol)  ΔSo (cal/mol*K)
    P4-P6 domain of Group I intron  -28 ± 3  -91 ± 8
       -4.1 ± 2.3  -9.6 ± 5.7
   

 

Loops, Turns, Motifs - Sept 27th

Outcomes

  • Role of turns in protein structure and function
  • Nuaanced understanding of the types of turns and how they are categorized
  • Be able to resources (PDB file, Ramachandran Plot, phi and psi, and PDB sum) to determine the type of turn in a protein
  • Know definition of super secondary structure, domains, and fold and common types of each (Primarily Voet reading)
  • Understand the relationship between fold and the topological diagram

Reading (to be completed before class!)

Reading on Loops and Turns

  • 1) Whitford This first reading is very short but provides a nice introduction to the topic.
  • 2) Chou Analytical Biochemistry 2000
    • Read just through beta-turns
      • Note there is a mistake in the phi and psi angles for residue i+1 in the type II' turn in table I. They should be phi = 60o psi = -120o
  • 3) From EXPASY text Chp 1- The image of type I and II turns nicely compliment table I of Chou
    • 1.6.1 beta-turns (reverse turns)

Reading on Super Secondary Structure, Motifs, and Folds

  • 5) Voet  (B. Tertiary Structure, p249-p256
    • Focus of this reading is on
      • Motifs (supersecondary structure) 
      • Domains
      • Folds

6) Loops and Turns Pre-Assignment Worksheet

In Class Activities

  • Discussion of Chou and Voet readings
  • Turns and loops as secondary structure analyzed - using molecular modeling software get worksheet
    • Inspect the structures of 1HEW, 1TNF, or 1RCP
      • Identify two β-turns (according to the nomenclature of Chou), identify the residues in the turn, and discuss an stabilizing interactions in the turn.
  • Slideshow

Problems

  1. Topology and Turns (See Worksheet) - Due Wednesday next week (see assignment in Worksheet)

You can practice looking at turns and loops using the identified structures from this paper
Protein Structure 1973 Lewis
Go to table II. Find some of the identified β-turns and then confirm in DeepView using the PDB structures of those enzymes

Use PDBsum. Please try out this tool and compare to the answers you assigned for 4CHA and other proteins. Help with the Codes in PDBsum, ProMotif

 

 


 

Mb and Hb - Sept 30th

Outcomes

  • Describe the binding charcateristics of myoglobin (Mb) and hemoglobin (Hb)
  • Correlate the binding curve for Hb to its function
  • Describe cooperativity in general and for Hb specifically
  • Define and describe p50
  • Describe the how the conformational changes in Hb relate to cooperativity and its function
  • Apply your knoweldge about the structure and function of Hb to predict how changes in conditions (addition of BPG, acidity, and mutations in the structure) will lead to adaption and abnormalities

Reading (to be completed before class!)

Lehninger Chp 5, Sect. 5.1

Pre-Assignment

See Hb worksheet
(You can pick up the worksheet in my box (BROH312))

 

In Class Activities

  • Hb Worksheet (pick up the worksheet in my box (BROH312))

Problems
1, 2, 3, 4, 7, 8, 9

 

 


 

Hb Structure Function - Oct 2nd

Outcomes

  • Describe the binding charcateristics of myoglobin (Mb) and hemoglobin (Hb)
  • Correlate the binding curve for Hb to its function
  • Describe cooperativity in general and for Hb specifically
  • Define and describe p50
  • Describe the how the conformational changes in Hb relate to cooperativity and its function
  • Apply your knoweldge about the structure and function of Hb to predict how changes in conditions (addition of BPG, acidity, and mutations in the structure) will lead to adaption and abnormalities

Reading (to be completed before class!)

Lehninger Chp 5, Sect. 5.1

Pre-Assignment

See Hb worksheet
(You can pick up the worksheet in my box (BROH312))

 

In Class Activities

  • Hb Worksheet (continued from last time)
  • PowerPoint

Problems
1, 2, 3, 4, 7, 8, 9

 

 


 

Introduction to Enzymes - Oct 4th

Outcomes

  • Define rates equations and rate constants for 0-order, 1st, 2nd order elementary reaction steps
  • Describe reaction coordinate diagram for a catalyzed vs uncatalyzed reaction
    • Use reaction coordinate diagram to describe rate enhancement and rate determining step in enzyme catalysis
  • Classification of Enzymes
  • Describe how enzymes mediate catalysis
    • Transition-state stabilization
      • General acid-base catalysis
  • Describe molecular recognition between enzyme and substrate or transition state
    • Intermolecular forces
    • Hydrophobic Effect
    • Transition-state stabilization
  • Articulate why the shape of enzymes actives sites more precisely complement the transtion state rather than the substrate

Reading (to be completed before class!)

Lehninger Chp 6, Sect. 6.1-6.3 (page 201)

  • Know and understand all terms in bold
  • Table 6-3 (memorize)
  • Be able to label and define terms in figure 6.3
  • Know residues (Fig 6-9) that can act in general acid-base catalysts
  • Define initial velocity (Fig 6-10)
  • Understand the relationship between Fig 6-10 and Fig 6-11
  • Relate terms in M-M equation to Figure 6-12

Pre-Assignment

No assignment. Instead complete Hb worksheet and bring questions to class

In Class Activities

  • PowerPoint
  • Worksheet

Problems
TBD

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


 

Enzymes Kinetics - Oct 7th

Outcomes

  • See outcomes from previous class
  • Know the Michaelis-Menten equation and how to apply it and linear versions to an understanding of the kinetic constants (kcat, Km, kcat/Km)
  • Be able to describe the meaning of (Vmax, kcat, Km, kcat/Km) and their reolationship to the qualities of an enzyme
  • Know how derive the M-M equation and the describe the underlying assumptions in the derivation
  • Be able to describe how experimental data (initial velocities) can be used to generate a M-M description of the enzyme kinetics

Reading (to be completed before class!)

Lehninger Chp 6, Sect. 6.1-6.3

  • Know and understand all terms in bold
  • Table 6-3 (memorize)
  • Be able to label and define terms in figure 6.3
  • Know residues (Fig 6-9) that can act in general acid-base catalysts
  • Define initial velocity (Fig 6-10)
  • Understand the relationship between Fig 6-10 and Fig 6-11
  • Relate terms in M-M equation to Figure 6-12

Pre-Assignment

Pre-Assignment activities on Worksheet for Enzyme Catalysis (please email photos of your answers) and be prepared to show your reading log in class.

In Class Activities

  • Worksheet on Enzyme Catalysis
  • Lecture Notes on Enzyme Kinetics (M-M equation)

Problems

  • All Post-Activity Exercises on Enzyme Catalysis Worksheet
  • All Post-Activity Exercises on Enzyme Kinetics Worksheet
  • Lehninger Chp 6: 6, 7, 8, 9

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


 

Enzyme Inhibition - Oct 9th

Outcomes

  • Utlilize various graphical representations of the M-M rate equation to distinguish between mechanisms for multiple substrate reactions
  • Utlilize various graphical representations of the M-M rate equation to determine inhibition type
  • Determine Km, Vmax, and the inhition constant Ki using plots of the M-M equation
  • Discuss the relationship between substrate binding site and active site and the values of Vmax and Km

Reading (to be completed before class!)

Lehninger Chp 6, Sect. 6.3 (Inhibition covered from 206-212)

  • Know and understand all terms in bold
  • Match Inhibition type to representations in Fig 6-17
  • Understand terms in Equations 6-28, -29, -30)
  • Know tests for Dtermining Inhibition Mechanisms Box 6-2

On Reactions with Two or More Substrates

  • Know terms in bold
  • Know how to interpret
    • Fig 6-13
    • Fig 6-14

Pre-Assignment

Pre-Assignment activities on Worksheet forInhibition (please email photos of your answers) and be prepared to show your reading log in class.

In Class Activities

  • Worksheet on Inhibition
  • Slideshow on using LB plots to distinguish types of Inhibition and and types Multiple substrate reactions

Problems

  • All Post-Activity Exercises on Enzyme Inhibition Worksheet
  • Lehninger Chp 6: 6, 7, 8, 9, 10, 11, 13, 14 (use Excel), 21, 24

 

 


 

Carbohydrates - Oct 14th

Outcomes

  • Recognize and describe structural features of carbohydrates that contribute to their structural diversity
  • Describe how proteins and carbohydrates interact and explain the biological role of those interactions
  • Correlate the structural features of carbohydrates to their function

Reading

Lehninger 7.1-7.2 (we willl cover 7.3 and 7.4 at a later stage)

  • Know Bold terms in section 7.1, Know and draw structures in Fig 7-1, Understand Fisher Projections, identify epimers in Fig 7-3, Perform 7-6 for any hexose, Draw Haworth from Fisher, understand Hemiacetals vs hemiketals vs acetals vs ketals, electrophile and nuceophiles in sugars.

Suggested Reading Berg 5th ed, CHP 11

Problems

Lehninger: 2*, 4, 6, 7, 8**, 9***, 13, 14, 17, 18, 22***, 24*****, 26

*(no need to memorize, just be able to do this one using resources)
** (use structures to help with your show your answer to this one)
***(draw the two diffrent forms of fructose)
****(be sure to use the structure in your answer)
*****(draw just two)

Berg 5th ed
Chp11 1, 2, 3, 4, 8, 12

In Class Activity

Group Problem Carbohydrates (through Lectins and Selectins)

Slideshow on Carbohydrates

 


Membrane Structure Oct 29th

Reading

Lehninger Chp 11: 11-1, 11-2,

Reading Notes and Questions

Additional Optional Reading Berg 5th ed: Chp12: Intro --12.1--12.2--12.3--12.4--12.5--12.6--12.7-- Summary

PreAssignment

  • Read and take notes on the chapter sections in Lehninger above
  • In Class open note short Quiz on the reading (link)

Required Resources

  • Presentation on Lipid Bilayers (Nice!)
    PLEASE DO THIS!
  • 2MLS
    Membrane Bilayer complex with Matrix Metalloproteinase-12

Problems

Berg Chp 12 5th Ed: 3, 4, 5, 7, 8, 9, 11

Lehninger Chp 11: 9, 10, 12, 13, 14, 15

Hydropathy Problem to turn in for 10 pts

 

In-Class activity

Worksheet on Membranes (Handed Out in Class)


 

 

 

   

Membrane Transport Systems - Nov 4th

Reading (to be completed before class!)

Required: Chp 11.3

Reading Notes and Questions

Supplemental reading and activities
Berg 5th: Chp 13
Intro - Sect 13.1- Sect 13.2- Sect 13.3
Sect 13.4 - Sect 13.5 - Sect 13.6
Summary

PreClass Quiz

On Moodle: MembraneTransport

In Class Activities

Group Worksheet ...... Key Membrane Transport

Worked Problem -  Cell Potential Problem        Key

Problems/Questions

Lehninger Chp 11: 13, 14, 15

Berg Chp 13 5th Ed: 10, 11, 14, 19


Additional Web Resources

Active Transport

Facilited Diffusion

Potassium Channels

   

P-type transporters - Nov 8th

Reading

Lehninger, P-Type ATPases, p413-415
The E. coli BtuCD structure: a framework for ABC transporter architecture and mechanism.

PreAssignment

No PreAssignment

Problems/Questions

Lehninger Chp11: 17, 21

In Class Activities

Discuss Figures 11-34, 11-35 in Lehninger and

Figure 1 from article Calcium Activation of the Ca-ATPase Enhances Conformational Heterogeneity

 

   

FRET! Nov 11th and 13th

Reading

Lehninger, Box 12-3 (FRET special section), pages 448-449.

FRET (quick intro)

Campbell, Biophysical Techniques, pages 193-196.

From Lakowicz's Principles of Fluorerscence Spectroscopy

Szabo Fluorescence Spectroscopy *goes with Slides below

Homework

Cambell Problems: 5.5.1, 5.5.2, 5.5.3, 5.5.5, 5.5.6 (solutions)

 

Additional (Due At Exam Time): 15 pts   This will soon be added to Moodle.

Access the article “Real-time monitoring of cyclic nucleotide signaling in neurons using genetically encoded FRET probes.” Brain Cell Biology. 2008, 36, 3.

Read the introduction, then look at the indicated figures to answer the questions below.

  1. The system you will be examining in the next question is shown in Figure 1B. What enzyme activity is being monitored? Is this upstream or downstream of cAMP signaling?
  2. Will FRET transfer increase or decrease during cAMP signaling?
  3. Now examine Figure 4. What ratio is being monitored? Is it higher or lower during cAMP signaling?
  4. How do the various neurotransmitters affect this ratio? What does this mean for cAMP signaling?
  5. Do all of the cells react the same? (How awesome is it that they can monitor all of them at once?!)

PreAssignment: FRET PreAssignment (Complete the preQuiz On Moodle)

In Class

In Class Worksheet ----- (solutions)

Slides

 

Signal Transduction Nov 15

Reading

Lehninger: Chp 12.1-12.3

Berg 6th ed: Chp14: 14.1-14.5 membrane structure

Introduction
Seven-Transmembrane-Helix Receptors and G Proteins
Phosphatidyl Inositol Bisphosphate and Phospholipase C
Ca2+, an intracellular messenger
Receptor Dimerization
Defects in Signaling Pathways
Signal-Transduction Pathways - Evolutionary Relationships
Summary

beta-adrenergic receptors (molecule of the month)

calmodulin (molecule of the month)

 

In Class Activities

PowerPoint Slides

Homework PROBLEMS

 

 

 

 

 

 

 

 

 

 

 

 

 


 

Methods I - Crystallography - Nov 17th

PreClass Assignments (to be completed before class!)


 

 

Problems

Electron Density Map Tutorial in Deepview

  • Do Lysozyme Tutorial and Fitting Residues into Denisty Tutorial

Additional Crystallography Problems Worksheet with key

Additional Handy Web Resources

X-ray diffraction