Pharmacology 400

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Pharmacology 400

• In silico
• Pharmacology

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• Dynamics
• Kinetics
• Drug Development

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Dynamics
Curve-fitting and modelling of agonist,
antagonist, inverse agonist, And ligand-binding
studies.
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Kinetics
Distribution and elimination of drugs.
Similarly, with intoxicants (poisons), although
this may include very long-term studies and Very
low levels of exposure. See FDA regulations on
environmental carcinogens ( baseline limit is
one extra cancer per 1,000,000 persons exposed
over 70 year lifetime ).
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Drug Development
Principal use of computing in pharmacology and
therapeutics. Structure-Activity studies and,
increasingly, high-speed screening and expert
systems for specialist study during development,
e.g., metabolism and bioavailability.
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Mibefradil surface1
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Mibefradil surface 2
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E4031 surface (COMFA)
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KCSA K channel
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KCSATEA
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Replacement of an intracellular loop of the
b2-adrenergic receptor with lysozyme stabilized
two flexible helices (5 and 6), allowing
crystallization of the fusion protein and
determination of the structure of this medically
important membrane receptor.
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Structure of the human b2-adrenergic receptor
(blue) embedded in a lipid membrane and bound to
a diffusible ligand (green), with cholesterol
and palmitic acid (orange) between the two
receptor molecules.
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Similar yet different. Rhodopsin (left) and the
b2AR (right) share overall structural features
and a binding pocket for their cognate ligands,
11-cis-retinal and carazolol, respectively (in
yellow), at a site located deep within the
transmembrane helices. However, the extracellular
loops are distinctly structured, a result that
may explain how diffusible ligands gain access to
the binding pocket in the b2AR.
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