Lec 6 LOs Flashcards
Determine the Kd value from a binding isotherm
DR/ Rt = D/ kD +D
When D = Kd Dr/rt = ½
- Only 50% of receptors are occupied here
When D «_space;Kd; Dr/rt = 0
When D»_space; Kd ; Dr/rt = 1
Calculate delta G from Kd or vice versa.
Use the equation
- delta G = -RTlnKd
- R is the gas constant ( 8.314 )
- T is the temp in Kelvin ( 273.15 + C )
Estimate the change in Kd from the change in delta G or vice versa.
The smaller the Kd, the stronger the binding
- Picomolar is the smallest and millimeter is biggest
Typically when using the equation stated above the change is really a 10 fold for Kd and 1.4 delta G change
Explain the characteristics of the type of interactions between drugs and receptors.
Hydrophobic interactions
Electrostatic interactions
Hydrogen bonding
Interactions with aromatic rings
what are hydrophobic interactions
attraction with nonpolar groups in water
- these interactions minimze the area of nonpolar bonding
- most common between protein-ligands
—. weak but abundant
Amino Acids
— aliphatic: Ala, Val, Leu, lle, Met, Pro
— aromatic: Phe, Trp
what are the electrostatic interactions
charge-charge
– + and - interactions
– operate over long distances
– amino acids
— Cationic: Lys, Arg, His
— Anion: Asp, Glu, Cys
ion-dipole & dipole-dipole
– water is dipole
– dipoles in proteins, backbone amine, and alpha helix
what is hydrogen bonding?
occurs between 2 electronegative atom
- distance between 2 of them is typically 2.7-3.2
- sensitive to orientation and overlapping orbitals
- ionic h-bonds are stronger than neutral ones
what are the different interactions with aromatic rings
attractions between electron rich (red) and electron deficient (blue) regions
- pi stacking
– parallel stacking of aromatic rings
– stacking in DNA double helix
- T stacking
– edge to face interaction
- cation-pi interaction
– interaction between a + charge and aromatic ring
