Drug Design and Development
The drug development process is divided into two parts:
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Discovering the candidate molecule
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Developing the new product
Drug requirements:
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Safety
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Effectiveness
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Specificity and selectivity
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Tight binging of the target
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Biological availability
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Easy to synthesize
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Size and solvability
The drug development process is composed of four phases:
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Safety check on healthy people
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Testing on a small group of patients
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Testing on a large number of patients
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Post marketing surveillance
The whole process takes 12-17 years.
Docking of a drug onto a receptor
When trying to design a good drug, it
is assumed that the drug is geometrically complementary to
the receptor.
The 3-D structure of the receptor is not always
known, so the best way to design a complementary ligand is to model the
functional groups in the drugs.
There are several methods to achieve this:
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Building a conformation library. Problem: The drug
may adopt a different conformation when bound to the receptor.
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Keeping a number of low energy conformations. Problem:
Time and space requirements.
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Sampling all the conformation space.The drug is a
small molecule, so it is possible to sample its conformational space and
find the energetically most favorable conformation. Problem: Lots of time
and space required.
The information used to calculate the conformational
energy:
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Atoms
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Group centers and rings
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Hydrogen bonds donor/acceptor groups
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Charged groups
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Hydrophobicity