Biochemistry 2280A Lecture Notes - Lecture 6: Fibril, Steric Effects, Disulfide

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Biochem Lecture 6 September 20, 2013
Topic 4 continued
o Van der Waals force
Sum of attractive/repulsive forces between molecules (or between other
parts of same molecule), other than those due to covalent bonds/hydrogen
bonds/electrostatic interactions of ions with one another or with
neutral/charged molecules
Side chains having forces with other side chains
Force between two dipoles
Dipole: separate charges
o Ligand-binding proteins
Many proteins contain sites where ligands specifically bind and form a
“complex” with the protein
Ligand: molecule that can form this complex
Binding occurs through multiple weak forces
Can be extremely specific
o Heme-molecule in hemoglobin is the ligand in that case
o Ligand binding Dissociation constant
Pretend that you’re trying to target a specific protein and prevent cancer
with a new drug
You wanna make a molecule that binds to this protein and knock it out
of commission
Your goal is to design a ligand that will be as specific as possible you
want to have a tight interaction with the protein (concept of dissociation
constant)
If it doesn’t have a tight bond, it has what are called off-targeted effects
If the binding affinity is weak might bind to other essential
proteins and the effects may be toxic
Measure of the strength/affinity of the interaction (how tight does the ligand
bind to the protein)
It’s an equilibrium constant for a protein (P) binding ligand (L)
P + L = PL
Kd = ((P)(L))/(PL)
o Dissociation constant
Higher affinity = tight binding = small Kd
Units are moles/L (M)
Femtomole = fM = 10-15
o Protein complexes
“Complexes” means many proteins
Perform some specific job in the cell
Most proteins are in some type of complex
E.g. ribosome: protein synthesis
Complex of 50+ proteins and RNAs
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Document Summary

Topic 4 continued: van der waals force. Sum of attractive/repulsive forces between molecules (or between other parts of same molecule), other than those due to covalent bonds/hydrogen bonds/electrostatic interactions of ions with one another or with neutral/charged molecules. Side chains having forces with other side chains. Many proteins contain sites where ligands specifically bind and form a. Ligand: molecule that can form this complex. Can be extremely specific: heme-molecule in hemoglobin is the ligand in that case, ligand binding dissociation constant. Pretend that you"re trying to target a specific protein and prevent cancer with a new drug. You wanna make a molecule that binds to this protein and knock it out of commission. Your goal is to design a ligand that will be as specific as possible you want to have a tight interaction with the protein (concept of dissociation constant) If it doesn"t have a tight bond, it has what are called off-targeted effects.

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