Thermodynamic basis of protein-ligand interactions Flashcards
What happens if ligand is in significant excess?
When ligand concentration is equal to the dissociation constant, 50% of proteins will be occupied
Will kd be higher or lower if binding of ligand and protein is strong?
lower - the stronger the binding, the lower the dissociation and the lower ligand concentration needed to achieve 50% occupancy
What happens to water when protein-ligand conformation is formed?
Returns to bulk state
Are negative or positive values for enthalpy favourable?
Negative
Are negative or positive values for entropy favourable?
Positive
For the protein ligand interaction to be favourable, you need to put more energy in than energy you get out. True or false?
False - get more energy out of interaction than you put in
The more negative, gibbs energy, the stronger the interaction between protein and ligand and the more energy you get out of the interaction. True or false?
True
Is fixing the conformation of protein/ligand favourable?
No because this affects entropy and makes it more negative as there is less disorder (positive entropy is favoured)
Is breaking interactions of protein/ligand with water enthalpically favoured?
No - because you are putting energy in to break the bonds
Is forming interactions between ligand and protein enthalphically favoured?
Yes - formation of bonds releases energy
Are water molecules returning to bulk state entropically favoured?
Yes - as they are less ordered than when they were bonded to ligand/protein
Is fenofibrate a lipophilic or hydrophilic drug?
lipophilic
Is lisinopril a lipophilic or hydrophilic drug?
hydrophilic
Lisinopril has a large number of rotatable bonds. What consequence does this have on enthalpy?
A lot of energy will need to be put in in order to get it into a state where can bind to protein and also need to break bonds with water as it is hydrophilic
