Microstates to Macrostates
"Multiplicity"
What is: number of ways n indistinguishable objects can be arranged in N different states. W(n,N) = N!/(n!(N-n)!)
"Intermediate and reaction energy diagram"
what is: a stable or quasi-stable state that a system passes through during a process, often between the initial and final states of a reaction or transformation.
visual representation of the energy changes
during a chemical reaction, as the reactants are converted into products
"Homotropic allostery"
what is: allosteric regulator binds to catalytic site. Usually activators. (e.g., oxygen as allosteric effector – effector of hemoglobin)
"Boltzmann entropy"
what is:
entropy = the number of ways in which a system can be configured.
S = kB ln(W) >>> Stotal = S1+S2 = kB ln(W1*W2) = kB ln(Wtotal)
"Ensemble" & "Ensemble-averaged properties"
What is: a collection or list of different ways an entity (molecule) can exist.
Ensemble-averaged properties: the average value of the property over all members of the ensemble.
"Elementary step"
What is: a single step in a reaction mechanism, where a chemical reaction occurs in a single, indivisible process.
"Heterotropic allostery" and an example
Heterotropic allostery: allosteric regulator binds to non-catalytic site. It can either activate or inactivate the enzyme it binds to.
(e.g., carbon dioxide as allosteric effector – effector of hemoglobin)
K- & V-type enzymes
What is:
K-type: enzymes whose affinity for substrate changes (increase or decrease) as the conformational ensemble redistributes.
V-type: enzymes whose activity (kcat), along with substrate affinity, changes as conformation changes.
"Statistical weight"
and reference state
what is: the quantity of each ensemble member divided by the quantity of a reference state.
(reference state: one ensemble member; the quantity of which is compared to all others and whose statistical weight is always 1.)
"Binding curve & the way to plot it"
What is: plots of binding occupancy vs ligand concentration; reveals information about binding affinity
(strength of interaction between two molecules).
***population (0.0-1.0) vs. concentration (M)
"Positive & negative cooperativity"
what is:
Positive: protein-protein interaction (PPI) facilitate a stable complex.
Negative: PPI destabilize the complex. (nH < 1)
No cooperativity: lack of PPI in the complex. (nH = 1)
Competitive, uncompetitive & noncompetitive
What is:
Competitive: binds at the orthosteric site competitively with the endogenous agonist.
Uncompetitive: binds at an allosteric site, but only if the orthosteric site has an agonist bound. (binds to allosteric sites that appear upon conformation changes)
Noncompetitive: binds at an allosteric site. (binds to a permanent allosteric site)
"Partition function"
What is:
the sum of the statistical weights of all members of an ensemble
"Positive/negative allosteric modulator" or PAM, NAM, SAM
What is:
PAM (Positive Allosteric Modulators): bind at the allosteric site and increase the population of conformations that have a higher affinity for
the orthosteric ligand.
NAM (Negative Allosteric Modulators): bind at the allosteric site and
decreases the population of conformations that have higher affinity
for the orthosteric ligand.
SAM (Silent A. M.): compete with PAM/NAM & thus silencing them.
“GPCR”definition and key molecules it interacts with
What is: integral membrane proteins containing an extracellular amino terminus, seven transmembrane a-helical domains, and an intracellular carboxy terminus. Transmit signals from outside the cells to the inside.
Activation of G protein can affect the production of secondary messenger molecules (e.g., cAMP, DAG, IP3, etc.).
•cAMP (G protein) pathway
•β-arrestin pathway
Neither Compound 6 nor Compound 15 change the activity of the receptor by themselves.
(Compound 6 is a PAM; Compound 15 is a NAM.)