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BPS 2110: Mid Term 1 Answers
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BPS 2110 Intro to Bio-Pharm Mid Term 1 Answers (Corrected)
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BPS 2110 Intro to Bio-FarmMid Term 1 Answers
1. Various methods are used to discover leads in the drug industry.
a. What are the five general types of lead identification methods used in drug discovery? (5
points)
High throughput screening
Natural products
Rational drug design
De-novo design
Combinatorial chemistry
b. Which of the types in part a represent the three most commonly used methods used in the
drug industry? (2 points)
High throughput screening
Natural products
Rational drug design
c. List one advantage and one disadvantage for each of the methods you listed in part b. (6
points)
Some examples are provided. Many answers are possible.
i. First method (HTS)
Adv:
Can be done quickly
Has been proven to work (reliable), most drugs discovered this way
Leads often have simple structures (easier to do SAR or manufacture)
Leads may be exclusive to company (company database)
Disadv:
Generates lots of false positives
Collections contain lots of PAINS
Can take long time to eliminate false positives
Structural variety limited (limited to what is in the collection)
ii. Second method (Natural products)
Adv:
Has been proven to work (reliable)
Natural compounds often very potent
Often find new structures
Can use local info to find them (poisons, local medicines)
Can be available in large amounts (farmable, fermentable)
Often have novel mechanisms of action (not otherwise obvious)
Relies on academia (no cost to the company)
May not need to optimize
Company can market as “natural”
1
, Disadv:
Most of the “easy” ones have already been found (rate of discovery slower)
Sometimes difficult to get large amounts
Molecules may have complex structures (stereochemistry), difficult to make synthetic
versions
Limited by what nature gives you (may be hard to improve properties, modify
structures)
Searching by academia only (slower, public knowledge of lead)
May not know mechanism of action
iii. Third method (Rational drug design)
Adv:
Has been proven to work (reliable)
Knowledge of structure and/or mechanism tend to speed up research
Assays and other tools may already be available
Design for simple structures
Disadv:
Requires knowledge of structure and/or mechanism
Molecules may have complex structures (start with natural product)
May require development of assays and other tools
2. Non-bonding interactions help to maintain protein structure and control drug binding.
a. List the four types of non-bonding interactions in order from strongest to weakest (5 Points)
Electrostatics (ionic)
Hydrogen bonding
Dipole-dipole
Van der Waals (London or dispersion)
b. Describe two features of the strongest interaction type (2 Points)
Attraction between + and –
Strength depends on surrounding environment, stronger in non-polar environments
Non-directional
Strength depends on distance between charges
c. Describe two features of the weakest interaction type (2 Points)
Attraction between induced dipoles created by electron circulation
Strength depends on surface area (stronger with larger surfaces)
Important in many binding pockets
Non-polar environment improves the strength of the polar interactions
Can improve potency of drugs by facilitating de-solvation
Can improve potency of drugs by affecting equilibrium between free and bound drug
2
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