Protein-Ligand Binding & Interactions Flashcards
Ligand
a molecule bound reversibly (does NOT bind permanently) by a protein
a ligand can be any kind of molecule, including another protein, DNA, RNA, small
molecules
Cofactor
a non-protein molecule that is bound to a protein and is required for the protein’s
biological activity.
For example, metal ions, ATP.
(Sometimes with enzymes, the term
coenzyme is used instead).
prosthetic group
partner molecules that bind tightly (DOES bind permanently) to a protein
(example: heme)
apo protein
protein without cofactor(s) or ligand(s)
holo protein
protein with cofactor(s) or ligand(s)
RMSD
root mean square deviation
measures structural similarity
the lower the RMSD, the better similarity
Models for protein-ligand binding
lock and key, induced fit, conformational selection
lock and key
High specificity can be explained by the complementarity between the binding
site and the ligand
Con: model assumes that complementary surfaces are preformed (based on size, shape, charge, or hydrophobic/hydrophillic character)
induced fit
Conformational changes may occur upon ligand binding
allows for . . .
- tighter binding of ligand
- high affinity for different ligands
Both the ligand and the protein can change their conformations
ex: camodulin
conformational selection (aka population shift)
proteins have a set amount of conformations they can bind to ligands
depending on the commonality of the ligand, the protein will shift its conformations based on it.
ex: ubiquitin
Ka
equilibrium constant
[PL] / [P][L] = ka / kd
Kd
equilibrium dissociation constant
1 / Ka
difference between ka & Ka and kd & Kd
ka and kd describes the fraction of a pool of reactant that reacts in a given
amount of time
Ka and Kd describes when the process will reach the equilibrium
where the association and dissociation rates are equal.
fraction of occupied binding sites (θ)
θ = [L] / ( [L] + Kd )
How can you determine Kd experimentally?
can be determined graphically or via least-squares regression
Myoglobin’s function to oxygen
main storage oxygen protein
Hemoglobin’s function to oxygen
circulating oxygen-binding protein (oxygen transport)
coordinate bond
type of covalent bond where both electrons from the same atom
how is a coordinate bond different from a traditional covalent bond?
coordinate bond is where both electrons from one atom bond to another atom
covalent bond is where both atoms share one electron to bond.
homologs
descended from a common ancestor
can be orthologs or paralogs
orthologs
can be evolved from a common ancestral gene by speciation
paralogs
genes related by duplication within a genome
what is cooperative binding
happens when a protein has multiple binding sites
these binding sites must be able to interact with each other
what is cooperativity?
where first binding event affects affinity at remaining sites
