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Physical and Chemical Principles

Solutions Manual

Prepared by James Fraser and Samuel Leachman

Chapter 10
Chemical Potential and
the Drive to Equilibrium


True/False and Multiple Choice

1. Molecules move spontaneously from regions of low 7. During protein folding, the entropy of water:
chemical potential to regions of high concentration. a. increases
True/False b. decreases
c. is equal to the protein entropy change
2. The difference in chemical potential for a region d. is zero
with 500 mM of molecule B and a region with 1 M of
molecule B is equal to: Fill in the Blank
a. kBT ln(0.5)
b. 0 8. A region with a high chemical potential for molecule A
c. 1 has a _______ concentration of molecule A than a region
d. kBT ln(500) with low chemical potential.
e. kBT ln(1) Answer: greater/higher
3. The proton concentration in pure water at standard 9. To make a buffer, add a weak acid to its conjugate
state (298 K) is: _______.
a. equal to 14 Answer: base
b. always less than –7
c. the square root of the ion product 10. _____, ______, and ______ sidechains generally have
d. 107 a pKa less than 7.0. _______, ________, and ______
e. 81 kJ•mol–1 sidechains have a pKa greater than 9.
Answer: His, Asp, Glu; and Tyr, Lys, Arg
4. The melting temperature (TM) is the temperature at
which 100% of the protein molecules are unfolded. 11. The integral of the melting curve of heat capacity versus
True/False temperature yields the _____________ change of protein
5. Which of the following must be independent of
temperature when properly applying the van’t Hoff Answer: enthalpy change
12. The _______________ change for a reaction determines
a. Keq
the direction of spontaneous change.
b. ∆So
c. 1/T Answer: free energy or ∆G
d. pH
6. The pKa of a protein sidechain depends only on
the chemical identity of the sidechain, not on the 13. Two regions of an ideal dilute solution have a difference
surrounding environment. in concentration of potassium ions (K+). At 293 K, what
True/False is the difference in chemical potential between region

The Molecules of Life by John Kuriyan, Boyana Konforti, and David Wemmer © Garland Science
2 Chapter 10: Chemical Potential and the Drive to Equilibrium

1, with a concentration of 0.5 M K+, and region 2, which Answer:

has a concentration of 2 mM? a. Q = [C]/([A][B]2) = 0.5/(0.01 × 0.22) = 1250
Answer: b. The reaction will proceed towards the right
since Q < Keq.
∆µ = RT ln 18. The arginine-tRNA synthetase enzyme catalyzes the
reaction that charges a tRNA with the amino acid
0.002 M arginine:
= 8.31 J•K–1•mol–1 × 293 K × ln
0.5 M
ATP + arginine + tRNA AMP + PPi + arginyl-tRNA
= –13.5 kJ•mol–1
The value of the equilibrium constant is 1.13.
14. The difference in chemical potential for a particular At equilibrium, following an in vitro reaction, the
molecule between two regions of an ideal dilute concentration of ATP is 2 µM, of arginine is 500 mM, and
of arginyl-tRNA is 10 µM. The concentrations of AMP
solution is 5 kJ•mol–1. The region with the higher
and of PPi are 500 µM. What is the concentration of
chemical potential has a concentration of 200 mM.
What is the concentration of the molecule in the other
region at 293 K? Answer:
Answer: [500 × 10–6] [500 × 10–6] [RtRNA*]
K = 1.13 =
C2 [2 × 10–6] [500 × 10–3] [10 × 10–6]
∆µ = RT ln
C1 [RtRNA*] = 4.52 × 10–5 = 45.2 µM
0.2 M
5000 J•mol–1 = 8.31 J•K–1•mol–1 × 293 K × ln
x 19. The pKa of a weak acid is 5. What is the pH when
the concentration of the acid form is 0.5 M and the
0.2 M concentration of the conjugate base form is 0.05 M?
ln = 2.05
x Answer:
pH = pKa + log10([base]/[acid]) = 5 + log10(0.05/0.5) =
0.2 M
= 7.79 5 + log10(0.1) = 4
20. The pH of a 0.15 M propionic acid/0.1 M sodium
x = 25.7 mM
propionate buffer is 4.71. What is the pKa of propionic
15. A cell with an internal calcium ion (Ca2+) concentration
of 20 µM is placed in media with a Ca2+ concentration Answer:
of 70 mM. What is the difference in chemical potential pKa = pH – log([base]/[acid]) = 4.71 – log(0.1/0.15) =
for Ca2+ ions between the inside and outside of the cell 4.71 + 0.18 = 4.89
at 310 K? 21. Consider a protein with a surface-exposed histidine
Answer: residue in a pH 4 solution. What is the fraction of protein
molecules in which this histidine residue is charged?
Cin (Assume that the pKa is 6.0.)
∆µ = µin – µout = RT ln
20 × 10–6 M [His]/[His+] = 10(pH – pKa) = 10(4 – 6) = 10–2 = 0.01
∆µ = 8.31 J•K–1•mol–1 × 310 K × ln Fraction[His] = [His]/[His+] / ([His]/[His+] + 1) = 0.9901
70 × 10–3 M
Therefore, 99% of the sidechains will be charged.
∆µ = 21.0 kJ•mol–1 22. For a protein with a surface-exposed aspartic acid,
at what pH will this residue be neutral in 75% of the
16. At equilibrium, in a test tube, the concentration of GDP protein molecules? (Assume that the pKa is 4.0.)
is 1 M, of GTP is 20 µM, and of Pi is 1 M. What is the
equilibrium constant of the reaction, GTP GDP + Pi?
[Asp–]/[Asp] = 0.25/0.75 = 1/3
Answer: pH = pKa + log(1/3)
[1][1] pH = 4 – 0.48
K= = 50000 pH = 3.52
[20 × 10–6]
23. A histidine is involved in an interaction with a glutamic
17. The reaction, A + 2B C, has an equilibrium constant of acid that stabilizes the charged form of the histidine,
2000. During a reaction, the concentration of A is 0.01 such that the value of ∆Go for deprotonation is 15
M, of B is 0.2 M, and of C is 0.5 M. kJ•mol–1 at pH 7.0 and 293 K (calculated using the
a. What is the reaction quotient (Q)? biochemical standard state). What is the pKa of this
b. In what direction will the reaction proceed? histidine?

The Molecules of Life by John Kuriyan, Boyana Konforti, and David Wemmer © Garland Science
Answer: 27. In the hydrophobic core of a folded protein, there are
[His]/[His+] = e(–∆G/RT) = e(–15,000/(293 × 8.31)) = 0.002118 three alanine and five phenylalanine residues that are
pKa = pH – log([His]/[His+]) = 7 – log10(0.002118) = 9.67 buried, and do not interact with water. Assume:
24. At the TM of a protein (55°C), the value of ∆Hounfolding is • In solution, waters can take on seven energetically
15 kJ•mol–1. What is the value of ∆Sounfolding? equal states.
Answer: • Two waters are ordered around each alanine in the
∆Sounfolding = ∆Hounfolding/TM = 15 kJ•mol–1/328 K = unfolded state.
45.7 J•mol–1•K–1 • Six waters are ordered around each phenylalanine
in the unfolded state.
25. A protein has a ∆Hunfolding value of 140 kJ•mol–1 at 25°C. • In the unfolded state, waters are ordered around
The value of ∆CP is 7.5 kJ•K–1•mol–1. The value alanine or phenylalanine residues and can take on only
of ∆Hounfolding at the TM is 230 kJ•mol–1. What is the two energetically equal states.
value of TM?
What is the difference in the entropy of the water due
to the burying of these residues as this protein folds?
∆CP (298 K – TM) = ∆Hounfolding @ 25 – ∆Hounfolding @ TM
298 K – TM = (∆Hounfolding @ 25 – ∆Hounfolding @ TM)/∆CP
Total water molecules = 2 × number of Ala +
TM = –[(∆Hounfolding @ 25 – ∆Hounfolding @ TM)/∆CP – 298 K]
6 × number of Phe
TM = 310 K or 37°C
26. A lysine sidechain has four torsion angles, each of = 36 waters
which can take on three different values (60°, –60°, and Sfolded = R ln736 = 8.31 J•K–1•mol–1 × 36 × ln7 =
180°). Each unique combination of angles is called a 582 J•K–1•mol–1
rotamer. For example, a lysine residue where the first, Sunfolded = R ln236 = 8.31 J•K–1•mol–1 × 36 × ln2 =
second, third, and fourth torsion angles are all 60° is 207 J•K–1•mol–1
one unique rotamer, whereas a residue where the first, ∆So = Sfolded – Sunfolded = 375 J•K–1•mol–1
second, and third torsion angles are 60° and the fourth 28. Why do proteins denature at cold temperatures?
torsion angle is 180° is a second rotamer.
In contrast, a serine sidechain has only one torsion While the physical mechanism behind cold denaturation
angle, which can take on three different values. is not yet understood, the phenomenon can be
Assume that all possible dihedral angles are allowed predicted from the curvature of protein stability curves.
at each angle for residues at this surface-exposed The constant curvature, arising from the difference in
position. heat capacity between the folded and unfolded states,
means that because ∆Go = 0 at the TM, it must also
a. What is the difference in molar entropy between a equal zero at some other point.
protein with a surface-exposed lysine and an otherwise
identical protein with a serine mutation at that position? 29. How do hydrophobic interactions provide favorable
b. Why might the simplification that each lysine entropy for protein folding?
torsion angle is able to adopt any of the three staggered Answer:
positions, independent of the conformation at other Since water molecules cannot hydrogen bond with
torsion angles, lead to an overestimate of the number of hydrophobic groups on the protein, the rotation of
low-energy conformations that lysine can adopt? water around these groups is restricted. When the
Answer: hydrophobic groups collapse into the core of the
a. protein, water no longer surrounds them. Thus, the
WK = 34 water that previously was restricted around the
hydrophobic groups is released to the bulk solvent and
WS = 31 free to move between many configurations (increasing
the entropy of the system).
WK 34
∆S = R ln = 8.31 J–1•K–1•mol–1 × ln
WS 31

∆S = 27.4 J–1•K–1•mol–1

b. Some rotamers might be disallowed because

they sterically clash with other residues, so not all
independent conformations of torsion angles might be

The Molecules of Life by John Kuriyan, Boyana Konforti, and David Wemmer © Garland Science
4 Chapter 10: Chemical Potential and the Drive to Equilibrium

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