GMS 6504 COMPREHENSIVE EXAM 2026 QUESTIONS AND
ANSWERS SCORED A+
✔✔What are the two conformations of a target protein - ✔✔tensed (T) or relaxed (R)
one
✔✔What is the Concerted Model - ✔✔A conformational change in one subunit requires
the same conformational change in all subunits (all are either R or T).
Binding of an allosteric modulator to an allosteric site can alter the equilibrium between
the R or T forms, which can in turn influence ligand binding to the orthosteric site.
✔✔What is the Sequential Model - ✔✔Induced fit: When a subunit binds a ligand it
induces a conformational change in that subunit from the T to R state
The ligand-induced conformational change from T to R favors ligand binding (and thus
the T to R transition) of adjacent subunits, but does not require it (i.e. subunits within a
multimer can exist as "all T", "all R", or a mixture of subunits in the T or R
conformations).
✔✔What are the types of protein kinase inhibitors? - ✔✔Orthosteric - a competitive
inhibitor that blocks the binding site
Allosteric Direct - induces a conformational change that blocks ATP binding
Allosteric indirect - induces a conformational change that blocks the protein substrate
binding site
✔✔ What are System Independent Parameters? - ✔✔Affinity
Efficacy
✔✔What are the parts of a system that are identified as System Dependent
Parameters? - ✔✔Number of receptors
Cellular machinery
Presence of other drugs
- Competitive
- Noncompetitive
✔✔Affinity is - ✔✔Thermokinetic propensity of drug to bind to receptor
Based largely on ΔG
✔✔Efficacy is - ✔✔Magnitude of change of receptor shape/function upon drug binding
Based on atom/atom interactions
, ✔✔What is the Occupancy Theory? - ✔✔Response is proportional to fraction of
receptors that are occupied
100% response is obtained when all receptors have ligand
✔✔What formula do we use to predict occupancy? - ✔✔Langmuir equation
DR/Rt = r = D/D+Kd
✔✔How do we define response effect? - ✔✔A+R --> (AR)
✔✔Intrinsic activity is depicted as what letter?
How is it defined? - ✔✔Alpha
Multiplication factor describing ability of agonist to produce a stimulus
✔✔In terms of intrinsic activity, what is determined to be a full agonist? - ✔✔α = 1
✔✔In terms of intrinsic activity, what is determined to me a partial agonist? - ✔✔0 < α <
1
✔✔In terms of intrinsic activity, what is determined to be an antagonist? - ✔✔α = 0
✔✔What is the formula for the estimation of relative efficacy? - ✔✔R = f ( α x r x Rt )
f = stimulus response
Rt = receptor number
✔✔What is the Two State Theory? - ✔✔Binding of a ligand to a receptor causes a
conformational change
A + R --> <-- AR closed --> <-- AR open
Receptors can spontaneously open
The ligand can bind to either open or closed receptor
✔✔What is the Ternary Complex Model? - ✔✔Developed to describe interactions
between ligand/receptor/G protein
Receptor activates G protein binds, becomes activated, leaves
A+R --> <-- AR + G --> <--ARG
ANSWERS SCORED A+
✔✔What are the two conformations of a target protein - ✔✔tensed (T) or relaxed (R)
one
✔✔What is the Concerted Model - ✔✔A conformational change in one subunit requires
the same conformational change in all subunits (all are either R or T).
Binding of an allosteric modulator to an allosteric site can alter the equilibrium between
the R or T forms, which can in turn influence ligand binding to the orthosteric site.
✔✔What is the Sequential Model - ✔✔Induced fit: When a subunit binds a ligand it
induces a conformational change in that subunit from the T to R state
The ligand-induced conformational change from T to R favors ligand binding (and thus
the T to R transition) of adjacent subunits, but does not require it (i.e. subunits within a
multimer can exist as "all T", "all R", or a mixture of subunits in the T or R
conformations).
✔✔What are the types of protein kinase inhibitors? - ✔✔Orthosteric - a competitive
inhibitor that blocks the binding site
Allosteric Direct - induces a conformational change that blocks ATP binding
Allosteric indirect - induces a conformational change that blocks the protein substrate
binding site
✔✔ What are System Independent Parameters? - ✔✔Affinity
Efficacy
✔✔What are the parts of a system that are identified as System Dependent
Parameters? - ✔✔Number of receptors
Cellular machinery
Presence of other drugs
- Competitive
- Noncompetitive
✔✔Affinity is - ✔✔Thermokinetic propensity of drug to bind to receptor
Based largely on ΔG
✔✔Efficacy is - ✔✔Magnitude of change of receptor shape/function upon drug binding
Based on atom/atom interactions
, ✔✔What is the Occupancy Theory? - ✔✔Response is proportional to fraction of
receptors that are occupied
100% response is obtained when all receptors have ligand
✔✔What formula do we use to predict occupancy? - ✔✔Langmuir equation
DR/Rt = r = D/D+Kd
✔✔How do we define response effect? - ✔✔A+R --> (AR)
✔✔Intrinsic activity is depicted as what letter?
How is it defined? - ✔✔Alpha
Multiplication factor describing ability of agonist to produce a stimulus
✔✔In terms of intrinsic activity, what is determined to be a full agonist? - ✔✔α = 1
✔✔In terms of intrinsic activity, what is determined to me a partial agonist? - ✔✔0 < α <
1
✔✔In terms of intrinsic activity, what is determined to be an antagonist? - ✔✔α = 0
✔✔What is the formula for the estimation of relative efficacy? - ✔✔R = f ( α x r x Rt )
f = stimulus response
Rt = receptor number
✔✔What is the Two State Theory? - ✔✔Binding of a ligand to a receptor causes a
conformational change
A + R --> <-- AR closed --> <-- AR open
Receptors can spontaneously open
The ligand can bind to either open or closed receptor
✔✔What is the Ternary Complex Model? - ✔✔Developed to describe interactions
between ligand/receptor/G protein
Receptor activates G protein binds, becomes activated, leaves
A+R --> <-- AR + G --> <--ARG
