AMATH 423/523 Mathematical Analysis in Biology and Medicine Winter 2023
Homework # 5
(Due February 23, Thursday, 11:59pm)
1. In a feedback control system governed by
du1
= f (un ) − k1 u1 ,
dt
duj
= uj−1 − kj uj , j = 2, 3, · · · , n;
dt
the feedback function is given as
a + um 1
(i) f (u) = , (ii) f (u) = ,
1 + um 1 + um
where constants a, m > 0.
(a) Determine which of these represents a positive feedback control and which a negative
feedback control.
(b) Determine the steady states and show that with positive feedback multi-stability is
possible while if f (u) represents negative feedback there is only a unique steady state.
2. Consider the system of nonlinear chemical reaction
1 k 2 k 3 4 k k
A −→ X, B + X −→ Y + D, 2X + Y −→ 3X, X −→ C,
where ks are the rate constants, and the reactant concentrations of chemical species A and
B are kept at constant values of a and b, respectively, for all time.
(a) Write the governing differential equation system, according to the law of mass
action, for the concentrations of X and Y ; nondimensionalize the equation so that they
becomes
du dv
= 1 − (β + 1)u + αu2 v, = βu − αu2 v,
dτ dτ
in which u and v are the corresponding variables for the concentrations of X and Y , τ =
k4 t, α = (k1 a)2 k3 /k43 , and β = k2 b/k4 .
(b) Determine the positive steady state and show that there is a bifurcation value βc =
1 + α at which the steady state becomes unstable in a Hopf bifurcation way.
√
(c) Show that in the vincinty of β = βc , the limit cycle has a period of 2π/ α.
3. The 3-state Markov system,
k1 k2 k3
GGGG
AF B GGGG
GBF B GGGG
GCF BG A, (1)
k−1 k−2 k−3
has been widely used in biochemistry to model the conformational changes of a single
protein undergoing though its three different states A, B, and C. For example, A is non-
active, B is partially active, and C is fully active.
February 17, 2023 Due February 23, Thursday, 11:59pm
AMATH 423/523 Mathematical Analysis in Biology and Medicine Winter 2023
(a) The probabilities for the states, p⃗ = (pA , pB , pC ), satisfies a differential equation
d
p⃗(t) = p⃗(t)Q,
dt
where Q is a 3×3 matrix. Write the Q out in terms of the k’s. Show that the sum of each
and every row is zero. Discuss in probabilistic terms, what is the meaning of this result?
(b) Compute the steady state probabilities pss ss ss
A , pB , and pC , and show that, in the steady
state, the net (probabilistic) flux from state A to B,
ss
JA→B = k1 pss ss
A − k−1 pB ,
is the same as the net flux from state B → state C, and also the net flux from C → A.
Since they are all the same, it is called the steady state flux J ss of the biochemical reaction
cycle in (1).
(c) What is the condition, in terms of all the k’s, for J ss = 0?
4. Consider single enzyme following Michaelis-Menten kinetic in which an E combines
with an substrate molecule S to form ES, and then drops a product molecule P and returns
E ∗:
k1 [S] k
GGGG
EF B ∗
G ES −→ E .
2
k−1
Let the probability for the three states of the enzyme E, ES, and E ∗ , at time t, be PE (t),
PES (t), and PE ∗ (t). They follow the system of differential equation:
dPE (t)
= −k1 [S]PE + k−1 PES ,
dt
dPES (t)
= k1 [S]PE − k−1 + k2 PES ,
dt
dPE ∗ (t)
= k2 PES .
dt
(a) We note that when the enzyme arrives at state E ∗ , it will remain there forever. What
is the probability distribution for the “random time” T from state E to state E ∗
FT (t) = Pr T ≤ t = PE ∗ (t),
and the probability density function
Pr t < T ≤ t + dt d
fT (t) = = FT (t)?
dt dt
(b) What is the mean time according to the distribution?
February 17, 2023 Due February 23, Thursday, 11:59pm
AMATH 423/523 Mathematical Analysis in Biology and Medicine Winter 2023
Additional Problems for AMATH 523
5. Consider the reaction system with two biochemical species X and Y which degrade
linearly, with rate constants b and d respectively, and X actives the synthesis of Y and Y
actives the synthesis of X according to
dx(t) ay 2
= 2 − bx,
dt k + y2
dy(t) cx2
= 2 − dy,
dt h + x2
where x(t), y(t) are the concentrations of X, Y at time t, and a, b, c, d, k and h are positive
constants. Nondimensionalize the system to reduce the relevant number of parameters.
Show that there can be two or zero positive steady states. [Hint: You might need to use
Descartes’ rule of signs.]
February 17, 2023 Due February 23, Thursday, 11:59pm
