Question

As discussed during the lecture, the enzyme HIV-1 reverse transcriptae (HIV-RT) plays a significant role for the HIV virus and is an important drug target. Assume a concentration [E] of 2.00 µM (i.e. 2.00 x 10-6 mol/l) for HIV-RT. Two potential drug molecules, D1 and D2, were identified, which form stable complexes with the HIV-RT.

The dissociation constant of the complex ED1 formed by HIV-RT and the drug D1 is 1.00 nM (i.e. 1.00 x 10-9 mol/l). The dissociation constant of the complex ED2 formed by HIV-RT and the drug D2 is 100 nM (i.e. 1.00 x 10-7 mol/l).
1. Compute the total concentration of [D1]tot that is needed to bind 90% of the HIV-RT at the given concentration [E]tot. Provide your answer as a numerical expression with 3 significant figures in the unit mol/l. You do NOT have to consider competition betwwen the drugs D1 and D2! They are administered separately.
2. Compute the total concentration of [D2]tot that is needed to bind 90% of the HIV-RT at the given concentration [E]tot. Provide your answer as a numerical expression with 3 significant figures in the unit mol/l.You do NOT have to consider competition betwwen the drugs D1 and D2! They are administered separately.

Answer 1

C)[D]/[ED] = 5.20

D)[D]/[ED] = 5.20

E)[D']_T = 1.495* 10 ^-7 M

F)[D'] / [ED'] = 0.0579

Explanation:

E = 250 nM =2.5* 10 ^-7 mol/L , T=298.15 K

Dissociation constant of K_D = 1.3 μM (1.3 *10 ^-6 M)

E + D ⇄ ED → K_a = [ED] / [D][E] (association constant)

ED ⇄ E + D → K_D = [E][D] / [ED] (dissociation constant)

C)

[E] =2.5*10^-7 mol/L

K_D = 1.3* 10^-6 M

K_D = [E][D] / [ED] → [D]/[ED] = K_D / [E]

= [D]/[ED] = 1.3* 10 ^-6 / 2.5 *10^-7

= 13/25 * 10

=130/25 = 5.20

[D]/[ED] = 5.20

D)

ΔG =RTln Kd

ΔG_2 for E and D = 1.987 * 298.15 * ln 1.3*10^-6

ΔG_2 592.454 * [ln 1.3 +ln 10^-6]

ΔG_1 = 592.424 [0.2623 - 13.8155]

ΔG_2 = -592.424 * 13.553

ΔG_1 = -8184.633 cal/ mol

ΔG_1 = -8184.633 * 4.18 J/mol = -34244.508 J?mol

ΔG_1 = -34.245 KL/mol

so, ΔG_2 = ΔG_1 - 10.5 KJ/mol

ΔG_2 = -34.245 - 10.5

ΔG_2 = -44.745KJ / mol

ΔG_2 =RT ln K_D

-44.745 *10^3

=8.314 *298.15 lnK_D

lnK_D' = - 44745 / 2478.81 g

ln K_D' = -18.051

K_D' = -18.051

K_D' = e^-18.051

[D]/[ED] = 5.20

E)

[E] = 2.5* 10 ^-7 mol/ L = a

K_D' = [E][D] / [ED'] E +D' → ED'

K_D' = a/2(x-(a/2) / (a/2)

KD' = x - a/2

=2.447 *10^-8 = (2.5/2) * 10^-7

x=2.447 * 10^-8 + 1.25 * 10^-7

x = 2.447 *10^-8 + 1.25 * 10 ^-7

x= 10^-7 [1.25 + 0.2447]

x = 1.4947 * 10^-7

[D']_T = 1.495* 10 ^-7 M

F)

K_D' = [E][D'] / [ED']

[D'] / [ED'] = KD' / [E]

[D'] / [ED'] = 1.447 *10^-8 / 2.5* 10^-7

[D'] / [ED'] = 0.5788 * 10^-1

[D'] / [ED'] = 0.0579

Step-by-step explanation:

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