University of Texas at Austin Regional — Protein Modeling

Protein Modeling · Division C · University of Texas at Austin Regional · 2020

117 questions · 290 points · 50 min· 13 questions from the original omitted

You have 50 minutes to finish this exam and the computer exploration of protein structure. This packet contains 60% of the overall score. The Exam is comprised of Section I and II. The exam accounts for 30% of the overall score. The Computer Exploration is comprised of Section III. The computer exploration accounts for 30% of the overall score. Each participant may bring one 8.5” x 11” sheet of paper that may be in a sheet protector or laminated that contain information without any annotations or labels affixed along with writing utensils for each participant. Anything written on the exam packet will not be graded. Only the answer sheet will be graded. Write your team number on every page of the answer sheet. Tiebreakers are labeled as ⟦TB#⟧. There are five tiebreakers in this exam.

I. Protein Biochemistry — Multiple Choice: Choose the most appropriate response for each answer. For questions that are multiple select, all the correct answers must be chosen to earn credit. No partial credit will be given for multiple select questions.

Question 1

2 pts

Which of the following is the most basic level of protein structure?

A. PrimaryB. SecondaryC. TertiaryD. Quaternary

Question 2

2 pts · select all that apply

In which of the following protein structures would hydrogen bonding between peptide -CO-NH groups and NH-OC occur? (Multiple select)

A. PrimaryB. SecondaryC. TertiaryD. Quaternary

Question 3

2 pts

Most proteins take what structure/shape once they have folded?

A. GlobularB. FibrousC. Alpha helicesD. Beta sheets

Question 5

2 pts

What will happen if a protein is not in the lowest energy conformation?

A. A protein will become denatured and stop functioning.B. A protein will continue to move and adjust until it finds its most stable state.C. A protein will stay at its current energy conformation.D. A protein will attempt to reach the highest energy conformation.

Question 6

2 pts

Which of the following statements below would be correct for a theoretical protein that has reached its conformation?

A. The interior of the protein would mostly contain amino acids like histidine, arginine and lysine.B. The interior of the protein would mostly contain amino acids like cysteine, glycine, and tyrosine.C. The interior of the protein would mostly contain amino acids like phenylalanine, leucine and tryptophan.D. The interior of the protein would mostly contain amino acids like aspartic acid and glutamic acid.

Question 7

2 pts

What should be the value of the Gibbs free energy of protein folding?

A. Positive (>0)B. Negative (<0)C. 0D. None of the above. Gibbs free energy is not used to describe protein folding.

Question 8

2 pts · select all that apply

Which of the following are techniques that could be used to study protein folding? (Multiple select)

A. X-ray crystallographyB. Fluorescence spectroscopyC. Circular dichroismD. Protein nuclear magnetic resonance spectroscopy

Question 9

2 pts

In one of Cyrus Levinthal’s papers, what was his estimation of the number of possible protein conformations?

A. 3³⁰⁰B. 4¹⁵⁴C. 1 x 10⁹D. 2¹⁰⁰

Question 10

2 pts

Which principle states that naturally evolved proteins have optimized their folding energy landscapes?

A. Law of conservation of energyB. Principle of minimal frustrationC. Levinthal’s paradoxD. Anfinsen’s dogma

Question 11

2 pts · select all that apply

Which of the following is/are component(s) of an amino acid? (Multiple select)

A. -NH₂B. -COOHC. CD. R group

Question 12

2 pts

What is the term for amino acids that have both the amine and carboxylic acid groups attached to the alpha carbon atom?

A. 1-,alphaB. 2-,alphaC. 3,-alphaD. 4,-alpha

Question 13

2 pts

What is the term for the carbon atom next to the carboxyl group?

A. α carbonB. β carbonC. σ carbonD. 𝝲 carbon

Question 14

2 pts

Which of the following amino acids below is considered achiral?

A. MethionineB. CysteineC. TyrosineD. Glycine

Question 15

2 pts

What is the term for the exact midpoint between two pKa values where the average net charge of all the forms present is zero?

A. IsomerismB. ChiralismC. ZwitterionsD. Isoelectric point

Diagram-based Questions: Answer the questions below referring to the diagram or ideas behind the diagram. Complete sentences are not required for this section.

FigureFor questions 16a, 16b, 16c, 16d, 16e

Question 16a

1 pt

What type of beta-sheet is shown above?

Question 16b

3 pts

Is this beta-sheet more stable than the other type? Explain your answer.

Question 16c

2 pts

What is the value of φ in this type of beta-sheet?

Question 16d

2 pts

What is the value of ψ in this type of beta-sheet?

Question 16e

3 pts

List an amino acid that are favored to be found in beta-strands in the middle of beta-sheets.

FigureFor questions 17a, 17b, 17c, 17d, 17e

Question 17a

1 pt

Who was the person who coined the term “funneled energy landscape”?

Question 17b

2 pts

In the funnel landscape, is the protein restricted to a single mechanism of folding or is the protein allowed to fold through a large number of pathways and intermediates?

Question 17c

2 pts

At which region of the funnel landscape does a protein have the highest energy state?

Question 17d

2 pts

What is the term for a point in the funnel landscape where the transition state for a protein is found?

Question 17e

1 pt

True or False: No protein could assume its native conformation without passing the transition state.

TrueFalse

Question 18e

2 pts

What conjugate acid of the imidazole side chain of this amino acid has what pK_a ?

FigureFor questions 19a, 19b, 19c, 19d, 19e

Question 19a

3 pts

What is the name of this structure?

Question 19b

2 pts

What is the typical bond dissociation energy of this structure in kcal/mol?

Question 19c

2 pts

Is this structure shorter or longer than a C-C bond?

Question 19d

2 pts

Is this structure formed in oxidizing or reducing conditions?

Question 19e

2 pts

Is this structure stable or unstable in the cytosol?

Label	Answer
A
B
C
D
E
F
G
H
I
J
K
L
M
N
O

II. DNA/RNA Structure and CRISPR-Cas Systems — Multiple Choice: Choose the most appropriate response for each question.

Question 21

2 pts

What is a nucleoside?

A. A ribose sugar connected to a base through the 1’C.B. A ribose sugar connected to a base through the 5’C.C. A deoxyribose sugar connected to a base through the 1’C.D. A deoxyribose sugar connected to a base through the 5’C.E. More than one of the above

Question 22

2 pts

Which chemical interaction is mostly responsible for the stabilization of the RNA secondary structure?

Question 23

2 pts

Which of the following on RNA causes it to self-hydrolyze?

Question 24

2 pts

Which of the following statements regarding the three-dimensional structure of DNA is correct?

A. The three-dimensional structure of DNA is the double helix.B. In DNA, the two-ring base is always paired up with the single-ring base.C. The two chains of DNA are held together by hydrogen bonding.D. The complementary base-pairing results in the base pairs being packed in the energetically most favorable arrangement in the interior of the double helix.E. More than one of the above

Question 25

2 pts

Which of the following contributes to the increased stability of DNA in comparison to RNA?

A. The phosphodiester bond is more susceptible to hydrolytic attack.B. The phosphodiester bond of DNA has a negative charge, which repels nucleophilic attacks by hydroxide ions.C. There is an extra hydroxide group on the 2’C of DNA.D. The phosphodiester bond of DNA has a positive charge, contributing to a stronger attraction between the base pairs.E. More than one of the above

Question 26

2 pts

Which CRISPR-Cas type(s) uses Cas6 endoribonuclease within the Cascade complex for primary processing of the pre-crRNA?

Question 27

2 pts

Which CRISPR-Cas type(s) requires crRNA, tracrRNA, and two domains of Cas9 (RuvC and HNH) for target cleavage?

Question 28

2 pts

Which CRISPR-Cas type(s) requires the annealing of the tracrRNA to the repeat sequences of the pre-crRNA and the subsequent cleavage of the dsRNA by the host RNase III?

Question 29

2 pts

Which of the following statement(s) about Type II CRISPR-Cas systems is correct?

A. The pairing between tracrRNa and precursor crRNA creates a single-stranded substrate claved by RNase III.B. The cleavage of DNA target in this CRISPR-Cas system type is the Cas9 protein.C. The formation of a complex with crRNA:tracrRNA drives Cas9 conformation changes that direct target DNA binding and cleavage in a PAM-independent manner as shown in recent studies.D. They require more Cas machinery for immunity than Type I and III systems.E. More than one of the above

Question 30

2 pts

Which of the following statement(s) about CRISPR-Cas9’s role in genetic engineering is correct?

A. The crRNa and tracrRNA can be combined into sgRNA, which is capable of guiding Cas9 to complementary sequences.B. The NHEJ repair pathway is considered to be more precise than the HDR pathway.C. A catalytically inactive Cas9 endonuclease can still be used as a DNA targeting module.D. The Cas9 endonuclease and sgRNA can be both engineering to create DSBs.E. More than one of the above

Question 31

2 pts

The spacer acquisition in Type I systems require the overexpression of which cas protein(s)?

Question 32

2 pts

Which of the following would you expect to bind tightly to dsDNA in a sequence-independent manner?

Question 33

2 pts

In which step of CRISPR immunity are CRISPR arrays transcribed and processed into crRNAs?

Question 34

2 pts

In which step of CRISPR immunity are new spacers acquired from exogenous nucleic acid into the CRISPR locus?

Question 35

2 pts

In which step of CRISPR immunity do crRNAs guide Cas nucleases for specific cleavage of nonhomologous sequences?

Short Answer: Answer the short answer questions below. The point values are indicated by the number in the parentheses. Complete sentences are not required for this section.

PassageFor questions 36a, 36b, 36c, 36d, 36e

There are drastic differences between the structure of DNA and RNA. Answer the following questions about these differences below.

Question 36a

1 pt

Which structure would have a narrow and deep structure in its major groove: DNA or RNA?

Question 36b

1 pt

Which structure would have a wide and shallow morphology in its major groove: DNA or RNA?

Question 36c

2 pts

There are at least how many forms of right-handed DNA double-helical structures?

Question 36d

2 pts

Which form of right-handed DNA double-helical structure is said to be the most stable in high humidity? (Hint: This structure was proposed by Watson and Crick).

Question 36e

4 pts

Why can RNA only form an A-type double helix?

PassageFor questions 37a, 37b, 37c, 37d, 37e

Answer the following questions about the biochemistry and structure of RNA molecules.

Question 37a

2 pts

How many hydrogen bonds can form between guanine and cytosine in RNA?

Question 37b

2 pts

How many hydrogen bonds can form between adenine and uracil in RNA?

Question 37c

2 pts

How many hydrogen bonds can form between guanine and uracil in RNA?

Question 37d

4 pts

Which two chemical interactions contribute to the folding of RNA into its three-dimensional structure?

Question 37e

2 pts

True or False: Noncanonical pairing and hydrogen bonding does not contribute to RNA folding.

TrueFalse

PassageFor questions 38a, 38b, 38c

There have been recent developments in CRISPR technology in terms of base-editing technology. These so called “second-generation genome-editing tools” can precisely convert a single base into another without causing double strand DNA breaks (DSBs). Answer the following questions about the evolution of second-generation CRISPR gene-editing tools.

Question 38a

10 pts

Komor et al. recently demonstrated that a fusion complex composed of nickase Cas9 fused with two other proteins can effectively convert Cytosine (C) to Thymine (T) at the target site without DNA DSBs. What are these two proteins?

Question 38b

5 pts

What is the name of the protein can be evolved and fused to nickase Cas9 to develop a base editor that achieves direct A-G conversion at the target sites?

Question 38c

5 pts

A complex resulting from the fusion of dCas9 and another protein can act as a gain of function screening tool. What is this protein fused with dCas9? (5) (Hint: This protein can convert cytosine to uracil through deamination).

PassageFor questions 39a, 39b, 39c, 39d, 39e

The incorporation of CRISPR-Cas9 systems in genetic engineering has increased in recent times. Answer the following questions about CRISPR-Cas9 and its scientific uses.

Question 39a

1 pt

Does CRISPR-Cas9 perform better in site selection in comparison to ZFNs and TALENs?

Question 39b

3 pts

How do most CRISPR-Cas9 systems express the guide RNA from a plasmid (Hint: What general promoter type is used?)

Question 39c

6 pts

What two additional structures are needed if we were to deliver Cas9 via viral vectors?

Question 39d

8 pts

How can scientists create an action similar to a DSB with 5’ overhangs (that is later repaired by NHEJ or HDR) by only introducing a single-strand nick into the target DNA?

Question 39e

2 pts

True or False: Despite the fact that each nucleotide within the 20 nucleotide protospacer contributes to the overall S. pyogenes Cas9 binding and specificity, single mismatches are still tolerated.

TrueFalse

Diagram-based Questions: Answer the questions referring to Figure 2.1 or ideas behind Figure 2.1. Complete sentences are not required for this section.

FigureFor questions 40a, 40b, 40c, 40d, 40e, 40f

Question 40a

3 pts

Determine the name of the alternative DNA structure shown for letter A.

Question 40b

3 pts

Determine the name of the alternative DNA structure shown for letter B.

Question 40c

3 pts

Determine the name of the alternative DNA structure shown for letter C.

Question 40d

3 pts

Determine the name of the alternative DNA structure shown for letter D.

Question 40e

3 pts

Determine the name of the alternative DNA structure shown for letter E.

Question 40f

3 pts

Determine the name of the alternative DNA structure shown for letter F.

III. Computer Exploration - Jmol — Directions: The following questions below is based on the crystal structure of cytidine deaminase from Burkholderia pseudomallei (3DMO.pdb). These questions are related to the structure of this protein. Answer these questions in the most concise and specific way possible. The point values for each question are addressed in the parentheses. (123) TB#5

PassageFor questions 41b, 41c, 41d, 41e

The following questions are based on residue 20.

Question 41b

3 pts

What is the XYZ coordinates of this atom on Jmol for atom number 1135?

Question 41c

3 pts

The side chain of this amino acid classifies it as a nonpolar aliphatic amino acid. What is the name of this side chain?

Question 41d

2 pts

True or False: This is the only proteinogenic amino acid with a secondary amine.

TrueFalse

Question 41e

2 pts

True or False: This amino acid is considered to be conformationally rigid due to its cyclic side chain.

TrueFalse

PassageFor questions 42a, 42b, 42c

The following questions are based on residue 4.

Question 42a

2 pts

What is the one letter name of this amino acid?

Question 42b

2 pts

Is the α-amino group of this amino acid protonated or deprotonated under biological conditions?

Question 42c

8 pts

Considering the structure of this amino acid, infer why it can participate in acid-base catalysis.

PassageFor questions 43b, 43e

The following questions are based on residue 38.

Question 43b

2 pts

State the IUPAC name of this amino acid.

Question 43e

2 pts

The benzyl side chain of this amino acid classifies the amino acid as what?

PassageFor questions 44b, 44c, 44d, 44e

The following questions are based on residue 78.

Question 44b

4 pts

The isopropyl side chain of this amino acid classifies it what?

Question 44c

10 pts

This amino acid is associated with sickle-cell disease. In sickle cell disease, a single glutamic acid in beta-globin is replaced with this amino acid (residue 78). As a result, the hemoglobin (Hb) is prone to abnormal aggregation. Based on your knowledge of the structure of this amino acid, infer why this mutation could lead to abnormal aggregation of Hb.

Question 44d

2 pts

Is the α-amino group of this amino acid protonated or deprotonated under biological conditions?

Question 44e

2 pts

Is the α-carboxylic acid group of this amino acid protonated or deprotonated under biological conditions?

PassageFor questions 45a, 45b, 45c, 45d, 45e

The following questions are based on residue 75.

Question 45a

2 pts

Identify the three letter name of this amino acid.

Question 45b

8 pts

Describe the side chain of this amino acid.

Question 45c

2 pts

What is the chemical formula of this amino acid?

Question 45d

2 pts

Is this amino acid polar or nonpolar?

Question 45e

2 pts

Is this amino acid charged or uncharged at physiological pH?

PassageFor questions 46a, 46b, 46c, 46d, 46e

Calculate the hydrogen bonds for the following (10) :

Question 46a

2 pts

Entire protein structure

Question 46b

2 pts

Residues 1-19

Question 46c

2 pts

Residues 28-39

Question 46d

2 pts

Residues 46-73

Question 46e

2 pts

Residues 82-88

PassageFor questions 47a, 47b, 47c, 47d, 47e

Calculate the struts for the following (10) :

Question 47a

2 pts

Entire protein structure

Question 47b

2 pts

Residues 4-6

Question 47c

2 pts

Residues 78-90

Question 47d

2 pts

Residues 54-66

Question 47e

2 pts

Residues 10-30

Question 48

2 pts

How many atoms are there for the helices present in this protein?

Question 49

2 pts

How many atoms are there for the sheets present in this protein?

PassageFor questions 50b, 50c, 50d, 50e

Answer the following questions about the overall protein structure (10) :

Question 50b

2 pts

How many hydrophobic atoms are there in the overall protein structure?

Question 50c

2 pts

How many charged atoms are there in the overall protein structure?

Question 50d

2 pts

How many hetero atoms are there in the overall protein structure?

Question 50e

2 pts

How many water atoms are there in the overall protein structure?

I. Protein Biochemistry — Multiple Choice: Choose the most appropriate response for each answer. For questions that are multiple select, all the correct answers must be chosen to earn credit. No partial credit will be given for multiple select questions.

Question 1

Question 2

Question 3

Question 5

Question 6

Question 7

Question 8

Question 9

Question 10

Question 11

Question 12

Question 13

Question 14

Question 15

Diagram-based Questions: Answer the questions below referring to the diagram or ideas behind the diagram. Complete sentences are not required for this section.

Question 16a

Question 16b

Question 16c

Question 16d

Question 16e

Question 17a

Question 17b

Question 17c

Question 17d

Question 17e

Question 18e

Question 19a

Question 19b

Question 19c

Question 19d

Question 19e

Question 20

II. DNA/RNA Structure and CRISPR-Cas Systems — Multiple Choice: Choose the most appropriate response for each question.

Question 21

Question 22

Question 23

Question 24

Question 25

Question 26

Question 27

Question 28

Question 29

Question 30

Question 31

Question 32

Question 33

Question 34

Question 35

Short Answer: Answer the short answer questions below. The point values are indicated by the number in the parentheses. Complete sentences are not required for this section.

Question 36a

Question 36b

Question 36c

Question 36d

Question 36e

Question 37a

Question 37b

Question 37c

Question 37d

Question 37e

Question 38a

Question 38b

Question 38c

Question 39a

Question 39b

Question 39c

Question 39d

Question 39e

Diagram-based Questions: Answer the questions referring to Figure 2.1 or ideas behind Figure 2.1. Complete sentences are not required for this section.

Question 40a

Question 40b

Question 40c

Question 40d

Question 40e

Question 40f

Question 41b

Question 41c

Question 41d

Question 41e

Question 42a