Topic 2 - Affinity Flashcards
When do drugs have an effect on a protein
When they are bound the protein is modified
Effect can still persist even when ligand leaves
What does binding affinity depend on
Higher number of complimentary interactions the more tighter the bond
Complimentary Interactions
Positive with Negative
Hydrophobic Interactions
Correct size and shape
What happens at equilibrium (Affinity)
Unbound Protein x Ligand will equal Complex
Or
Dissociation Rate Constant / Association Rate Constant
Or
Kd
What is Kd
A numerical value that represents the binding affinity the ligand has for a specific protein
The concentration of ligand needed to bind 50% of total receptors
What would an equilibrium of 2nm mean
At any given moment 2nm of receptors are bound.
Kon = Koff
When one complex dissociates another associates
Effects of:
Smaller Koff
Same Kon
Smaller Koff = Slower Koff
Ligand remains bound for longer
- More targets will be bound at equilibrium
- Takes longer to reach equilibrium
Lower Kd (Koff/Kon)
Effects of:
Same Koff
Larger Kon
Larger Kon = Faster Kon
Ligand in area is more likely to bind
- More targets will be bound at equilibrium
- Takes less time to reach equilibrium
What does a small Kd mean
More tightly the ligand binds
Higher affinity
What kind of graph is a Kd graph
Hyperbolic
Will be sigmoid on a log graph
How is concentration of ligand and targets bound related
The higher the concentration the more complexes formed
Slow off drug (What is it)
Drugs that remain bound for a long time
Slow off drug (Binding Equilibrium)
Takes a long time to reach binding equilibrium
Slow off drug (Effect on pharmacokinetics)
Drug can continue to have an effect even when most of the dose has left the body
Fast on drug (What is it)
Drugs that have a high likelihood of binding
