EXAM 1 - Properties of Drug: Target Interactions Flashcards
what is Kon and Koff?
Kon - the rate that the ligand and receptor bind to eachother
Koff - the rate that the ligand and receptor dissociate from eachother
Kd = ______
Kd = [receptor][ligand]/[receptor:ligand]
Kd tells you the binding affinity situation at equilibrium
as Kd becomes smaller, what happens to the receptor:ligand complex?
it increases
what is deltaG?
energy needed to bind
- total energy used or produced by binding event
- pos is endothermic/non-spontaneous
- neg is exothermic/spontaneous
What is deltaH?
enthalpy
E(break) - E(form)
- neg is more favorable
What is deltaS?
entropy - disorder
- loss of conformational freedom
- neg is unfavorable
characteristics of non-covalent interactions
- no electron sharing
- weak interactions between molecules
- exothermic reactions
- stabilize receptor:ligand complex
Describe ionic bonds
- strongest intermolecualr bond
- opposite charge attraction
- stronger interactions occur in hydrophobic envrionments
describe hydrogen bonds
- weaker than ionic but stronger than VDWs
- between electron deficient hydrogen and electron rich N or O
Describe van der Waals interactions
- the weakest interaction
- occurs between hydrophobic regions of the drug and target
- transient areas of high and low electron densities cause temporary dipoles –> binding
- must be close together
types of pi-pi interactions
benzenes stacked
benzenes displaced stacked
t-shape
- occurs when two aromatic systems are co-planar
- seen inserted into DNA
describe ion-dipole interactions
charge on one molecule interacts with dipole moment of another molecule
- stronger than dipole-dipole
describe induce-dipole interactions
- charge on one molecule induces a dipole on another molecule
- between quaternary ammonium ion and an aromatic ring
what type of bonding/interaction occurs in a pi-pi interaction?
a) hydrogen bonding
b) dipole-dipole interactions
c) van der Waals
d) ionic/electrostatic
c) van der Waals
Why is desolvation necessary?
- desolvation must occur before interaction between drug and target
- desolvation requires energy to remove water molecules
- the drug must have a higher affinity to the target than the solvent (water) for it to bind
how do polar groups affect desolvation?
polar groups on both the target and the drug increase hydrophilicity
- makes it harder to remove the water
How are hydrophobic interactions contribute to entropy?
- water molecules form an ordered layer around the hydrophobic membrane of the drug (negative entropy)
- when the drug binds to the target, the water molecules are ‘freed’
- increases entropy
- beneficial to binding energy
`Are covalent bonds used in drugs? why or why not?
covalent bonds are avoided because they are highly reactive, are less specific, and have permanent binding
- nucleophile on target and electrophile on drug
Steps of the composite binding model
1) solvated ligand must achieve bioactive conformation (the formation that properly presents the pharmacophore to the receptor)
2) solvated ligand removes water of solvation
3) ligand binds to site, providing free energy from interactions (increase entropy)
4) ligand dissociates from binding site
