1 of 2

Molecular polymorphism (solution)

7.4.P7
The biological roles of complex organic molecules are determined by their shape -- the way atoms and electrons create charge distributions on the
molecule's surface. As a result of those charge distributions, the molecules can interact in specific ways, attracting and sticking to each other or to
other organic molecules. For some proteins, their shape can be changed by the addition of a small amount of energy. Since different shapes can
result in different biological roles, the same molecule can play different biological roles if the energy needed to change their shape is not too large.
Since the probability of a molecule having a higher energy than its ground state in a thermal bath is proportional to the Boltzmann factor, e-E/kBT,
we will use this to generate estimates of the probability that a protein has a changed shape.
1. Let's call the normal (ground state) shape of a molecule (alpha). Suppose that adding an energy E to a molecule will change it to a new
shape, (beta). For the purposes of this problem we'll assume that this is a two-state system. The molecule has to be in either state or the
state . If the molecule is immersed in a thermal bath of temperature T, find an expression for the probability, P that the molecule will be in the
state and the probability P that the molecule will be in the state . Since there are only two states, your two probabilities should add to 1
(100%). Express each probability as a function of the symbol z = e-E/kBT.
Since the state alpha is the ground state, the excitation is 0. So its probability is proportional to the Boltzmann factor with a 0 in the
exponent, or e0 = 1. For the beta state, the excitation is E so the probability is proportional to the Boltzmann factor, with E in the
exponent, or z. The trick is these don't add up to 1. We have to divide by the total for getting anything = 1 + z. So we get

P = 1/(1+z) and P = z/(1+z).

These add up to (1+z)/(1+z) =1, just as they should.
2. If the thermal bath (cellular fluid) is at 300 K, and the excitation energy E needed to change the molecule's shape is 50 meV (milli-electron
volts), find the probability that the molecule will be in shape . (Hint: At 300 K, the value of kBT is about 1/40 eV.)
We need to calculate z, the exponential of -(50 meV)/(1/40 eV). Since 1/40 = 0.025, 1/40 eV = 25 meV, so we want
z = e-(50/25) = e-2 = 0.135
So our probability is

P = z/(1+z) = 0.135/(1.135) = 0.119

or about 12%.
3. Consider the limiting cases in order to see what range the probabilities can go over.
3.1 If the temperature were small (close to 0 K), what would the probability be that the molecule is in its ground state?
If the temperature is very small, then E/kBT would be very large. Then e raised to a large negative power would be very small -- close to
0. So z would be near 0 and the probability of being in the alpha (ground) state would be close to 1 -- 100%.
3,2 If the temperature were very large (approaching ), what would the probability be that the molecule is in its ground state?
If the temperature is very large, then E/kBT would be very small. Then e raised to essentially the power 0 would be very close to 1. So z
would be ~1 and the probability of being in the alpha (ground) state would be close to 1/(1+1) = 1/2 -- 50%.
These results make sense. When there is almost no thermal energy, the probability that the molecule gains enough energy to leave the
ground state is very small, so it almost always stays in the ground state (probability 1). When there is a lot of thermal energy, the energy
difference between the two states becomes negligible and the molecule can go back and forth from one state to the other easily. The
probability will then be equal that they are in each state. So overall, we expect the probability of the ground state to go between 1 and 1/2
as the temperature grows, and the probability of finding the excited state to go from 0 up to 1/2 as the temperature grows.
4. What value of E would a molecule need to have to be in shape one quarter of the time?
We can set the probability of one of the states equal to the known value, solve for z, and then take the log to get then energy. It's a (tiny)
bit easier to solve for the ground state since there is only one z in its expression, so let's solve
1/(1+z) =

2 of 2

Flipping both sides over gives

4/3 = 1+z
z= 4/3 - 1 = 1/3
Taking the natural log gives
ln(z) = ln(e-E/kBT) = -E/kBT = ln(0.333) = -1.10
so
E = 1.10 kBT.
Since we know kBT is equal to 25 meV, the energy gap would have to be 1.1 x 25 meV = 27.5 meV.
Joe Redish 1/28/16