The MOLECULES

of LIFE
Physical and Chemical Principles

Selected Solutions for Students

Prepared by James Fraser and Samuel Leachman

Chapter 2
Nucleic Acid Structure
Problems and Solutions
True/False and Multiple Choice
3 phosphate group and the hydrogen atom at the
2 position of the ribose ring in DNA. Compared with
DNA, RNA has the 2 hydrogen replaced by hydroxyl
group (OH) and the two oxygen atoms (2 ribose and
3 phosphate) repel each other strongly. Rather than
distorting the structure away from the Watson-Crick
model, it is energetically favorable for RNA to switch to
the C3 endo conformation.

2. Which of the following is not a stabilizing force for the

structure and stability of double-stranded nucleic acids?
a.
b.
c.
d.

base stacking
hydrogen bonding
disulfide bonds
electrostatic forces

4. Genomic DNA can become deformed from its normal

B-form by DNA binding proteins, such as the histone
proteins and the TATA-box binding protein.
True/False
6. Classify the following RNA structural elements as
secondary or tertiary structure:
a.
b.
c.
d.
e.
f.
g.

14. Label the atoms, the bases, the hydrogen bonds

across bases, the major and minor grooves, and the
interactions along the grooves for the following base
pair (oxygen and nitrogen atoms are not identified
Problem set (quantitative question 2) (na_56_v1)
explicitly):

coaxial helices
pseudoknot
hairpin
junction
adenosine platform
ribose zipper
bulge

Answer: Secondary: c, d, g; tertiary a, b, e, f

Fill in the Blank

8. The modified RNA base in which two methyl groups are
added to guanine is __________.
Answer: N,N-dimethylguanine. The corresponding
nucleoside is N,N-dimethylguanosine.
10. Hoogsteen base pairs, where the hydrogen-bonding
interactions utilize the Watson-Crick base-pairing edge
on one base and the major groove edge in the other
base, can be utilized to form an RNA _______ helix.

Is the base pair a standard Watson-Crick base pair?

2Q14

Answer:

H
H

minor groove

N
N

Answer: triple

Quantitative/Essay
12. What physical factors force RNA to adopt only the C3
endo sugar configuration, but allow DNA to adopt either
the C2 endo or the C3 endo sugar configurations?
Answer:
The C2 endo configuration results in close contact
(1.9 ) between one of the oxygen atoms of the

N
N

major groove

The Molecules of Life by John Kuriyan, Boyana Konforti, and David Wemmer Garland Science

Chapter 2: Nucleic Acid Structure

Interactions on minor groove: H-bond acceptor, H-bond
donor, H-bond acceptor.
Interactions on major groove: hydrogen atom, H-bond
acceptor, H-bond acceptor, H-bond acceptor.
The G-U base pair is not a standard Watson-Crick base
pair.

16. In water, why is base stacking relatively more important

than hydrogen bonding to forming a DNA double helix?
Answer:
Water can make H bonds with the DNA base H-bond
donor and acceptors, so the energetic gain in
interactions when those H bonds are satisfied by other
nucleotides is not great. However, the many small polar
interactions along the nucleotide rings that are formed
upon base stacking are energetically more favorable
than the interactions with water.
18. Why is the R (purine) in GNRA tetraloops required rather
than a pyrimidine?
Answer:
The R position, adjacent to the A in sequence and
space, is functionally significant because it provides
a large surface area (the base has the two rings of a
purine, as opposed to one ring for a pyrimidine) against
which the A can base stack.
20. Which of the following DNA sequences is most likely to
adopt the Z-form? Why?
a.
b.

22. The structure of the large ribosomal subunit from

Haloarcula marismortui (PDB code: 1FFK) has been
solved by x-ray crystallography. The 23S RNA contains
2922 nucleotides (758 A, 889 G, 739 C, and 536 U).
a. Assuming a random distribution of nucleotides,
how many four-mer sequences with the sequence G-N
(any base)-R (purine)-A are possible?
b. There are actually 21 GNRA tetraloops in
the structure. What percentage of possible GNRA
sequences actually formed tetraloops in the structure?
Answer:
a. Probability of G = total G/total nucleotides =
889/2922
Probability of N = 1.
Probability of R = (total A + total G)/total nucleotides =
(758 + 889)/2922.
Probability of A = total A/total nucleotides = 758/2922.
Each four-mer has a GRNA probability = (probability of
G) (probability of N) (probability of R) (probability of
A) = 0.0445.
Total four-mers = 2922 3 = 2919.
Probable GRNA four-mers = probability total four-mers
= 0.0445 2919 = 130.
b. If only 21 GNRA tetraloops formed out of a possible
130, then16% of the sequences form a stable tertiary
GNRA tetraloop motif.

GCGCGCGCATATGCGCGCGCC
AGAGAGCTCTCTCTCTAAAAT

Answer:
Sequence a is more likely to adopt Z-form because
it alternates purine and pyrimidines in a GC-rich
sequence. This alternating pattern of 2 endo and 3
endo puckers yields the zig-zag pattern, where the
smallest repeating unit is two base pairs, characteristic
of Z-form DNA.

The Molecules of Life by John Kuriyan, Boyana Konforti, and David Wemmer Garland Science