Protein- Ligand Interactions Flashcards
Why do most drugs fail pre clinically?
Target protein MOA is not robust
What is the most common protein for drugs to bind to?
G- protein coupled receptor
Do all drugs bind to proteins?
Most drugs
NOT all- E.g. cisplatin
What are proteins made up of?
Mostly Amino acids
type of bond interactions in order of strength decreasing?
Single Covalent bond > cation- anion > H-bonding > pi cation > pi-pi > dipole-dipole > London
Is the lock and key hypothesis flawed?
YES- assumes shape is rigid and if shape not exactly complimentary- won’t fit in
In reality- Ligand = flexible
Kd equation?
Kd= [P] [L] / [P] = moldm-3
When [L] = kd……?
[P] = [PL]- protein in 50% occupied
The stronger the binding the lower the conc of drug required to reach 50% occupied- T/F?
TRUE
Gibbs free energy?
🔺G = 🔺H - T🔺S
🔺H—> change in enthalpy
T—> temp
🔺S—> change in entropy
Interaction is favourable between P and L if 🔺G is +ve or -ve?
NEGATIVE
🔺G defines the……?
Strength of the interaction
The most -ve the value- the most more PL complex formed
Does ligand need to lose any interactions before binding to protein?
YES- E.g. with water
Put in energy to break
When interactions are formed , does that put energy in the system?
YES
Is the protein fixed shape or flexible?
Flexible but once bound to the ligand- fixed and the interactions with water are lost
