Problem 1: For most drugs the following changes occur upon binding to the biological target:
Answers:

• electron orbitals of the drug form bonding hybrid orbitals with the receptor atoms
• interactions with target atoms compensate for the lost water interactions and entropy changes
• electrons jump to excited electron orbitals upon drug binding
• level of bond vibrations in the drug changes

Problem 2: The strongest hydrogen bonds are formed upon one of these conditions
Answers:

• acceptor N, or O atoms are not polarized
• there are no other hydrogen bonds formed with the same acceptor atom
• the acceptor of the bond does not have exposed lone pair of electrons
• hydrogen attached to the hb-donor is very close to a lone-pair of an hb-acceptor

Problem 3: Drugs with one primary, secondary or tertiary amine group and no other basic or acidic groups have the following properties :
Answers:

• get predominantly positively charged at pH below pK_a of the amine group
• all statements are correct
• get predominantly neutral at pH above pK_a of the amine
• get the same amount of neutral and charged molecules at pH = pK_a

Problem 4: Which answer ranks sites by expected acidity pH value, from high/alkaline values to low/acidic?
Answers:

• blood plasma,duodenum,stomach
• blood, stomach, duodenum
• stomach,blood plasma,duodenum

Problem 5: Which number is closer to the dielectric constant of water at 300K?
Answers:

• 1.
• 0.013
• 80
• 7.9
• 20.
• 4.

Problem 6: The interaction energy between two charges q₁ and q_2, is directly proportional to
Answers:

• the product of the charges, q₁ x q₂
• the difference between the charges
• the sum of two charges q₁ + q₂
• the distance between the charges
• the ratio of the charges, q₁ / q₂
• the square root of the product, Sqrt(q₁ x q₂₎

Problem 7: The sidechain of the following residue carries net positive charge at physiological conditions:
Answers:

• Asp
• Ser
• Lys
• Val
• Gly
• Phe

Problem 8: The sidechain of the following residue carries a net negative charge at physiological conditions:
Answers:

• His
• Met
• Arg
• Glu
• Ile

Problem 9: Which statement about the buried charged atoms in folded proteins is valid? Consider only groups with total formal charge of +1 or -1, e.g. groups in Asp,Glu,Arg,Lys.
Answers:

• hydrogen bonds from proximal aminoacid sidechains stabilize single buried charges isolated from water
• buried charges are stabilized by hydrophobic interactions with the surrounding atoms
• buried charges are stable as long as they are not involved in salt bridges
• single buried charges in proteins are extremely rare and energetically unfavorable

Problem 10: In the process of drug-target complex formation, burying an unpaired hydrogen bond donor or acceptor away from the solvent upon binding has the following effect (choose the best answer):
Answers:

• does not contribute to the ΔG of binding
• makes a favorable (negative) contribution to the ΔG of binding
• leads to the donor/acceptor atom desolvation and thus lowers ΔG of binding
• makes an unfavorable (positive) contribution to the ΔG of binding

Problem 11: A drug is a weak acid with pKa of 4. Taken orally it is in a stomach solution of pH = 2 What balance of species will be found in stomach? (neutral = unionized).
Answers:

• 100 neutral and 1 positively charged
• 100 neutral and 1 ionized
• 10 charged and 1 neutral
• 100 ionized and 1 neutral

Problem 12: A drug is a weak base, it has the pKa of 8. It was taken orally and was absorbed in small intestine at pH = 6. What is the balance of charged and uncharged species in the intestine? (neutral = non-ionized).
Answers:

• 100 ionized to 1 neutral
• 10 neutral to 12 charged
• 100 neutral to 1 negatively charged
• 100 neutral to 1 ionized
• 1 charged to 10 neutral