PharmacologyAdvanced~18 min

Enzyme Kinetics Simulator

Michaelis–Menten, and how inhibitors give themselves away

Tune Vmax, Km, and inhibitor concentration across four inhibition mechanisms, and watch each one produce its own unmistakable signature on a Lineweaver–Burk plot.

The takeaway

You can determine where a drug binds without ever seeing it bind — the geometry of the double-reciprocal plot tells you the mechanism.

Michaelis–MentenKm and VmaxCompetitive inhibitionNon-competitiveUncompetitiveLineweaver–Burkkcat/Km
Read the theory: Targeted Protein Degradation

Inhibition mechanism

Km apparent

150.0µM

↑ 3.00× vs 50

Vmax apparent

100.0µM/min

= 100% of Vmax

kcat (turnover)

166.7s⁻¹

1.00e+4 substrates · enzyme⁻¹ · min⁻¹

kcat / Km

1.11 × 10⁶M⁻¹s⁻¹

specificity constant

Michaelis–Menten curve

v = Vmax·[S] / (Km + [S])

The hyperbola saturates: once every active site is occupied, more substrate buys you nothing. The dashed grey line is the uninhibited reference — the difference between the two curves is the drug's effect.

Inhibition at [S] = Km

50.0%

Surmountable by [S]?

Yes — Vmax recoverable

Intrinsic kcat

166.7 s⁻¹

Lineweaver–Burk (double reciprocal)

1/v = (Km/Vmax)·(1/[S]) + 1/Vmax

Linearise the hyperbola and each mechanism leaves a different fingerprint. Watch where the lines cross as you raise [I] — that intersection point is the whole diagnosis.

ConditionSlope (Km/Vmax)y-int (1/Vmax)x-int (−1/Km)
[I] = 00.5000.0100-0.0200
[I] = 20 µM1.5000.0100-6.67e-3
[I] = 40 µM2.5000.0100-4.00e-3

Competitive signature: Lines share the SAME y-intercept (1/Vmax is untouched) and fan out to different x-intercepts. A shared y-intercept is the fingerprint of competitive inhibition.

Mechanism · Competitive

Where does the inhibitor bind? Free enzyme (E) only — the active site

The inhibitor is a substrate look-alike that occupies the active site of the FREE enzyme. Enzyme and inhibitor compete for the same real estate, so the enzyme merely looks like it has lost affinity — apparent Km rises. Flood the system with substrate and you out-compete the inhibitor: Vmax is fully recoverable. This surmountability is the diagnostic hallmark.

Effect on Km

Km apparent ↑ by α

Effect on Vmax

Vmax unchanged

In the clinic: Methotrexate on dihydrofolate reductase (a folate mimic) and statins on HMG-CoA reductase (an HMG-CoA mimic). Both are active-site rivals.

Why pharma cares

Mechanism of action is not a marketing word — it is a measurement. You run the assay at several [S] and several [I], plot the double reciprocal, and the geometry of the lines tells you whether your molecule sits in the active site or somewhere else entirely.

  • Competitive drugs lose potency when the natural substrate piles up. A competitive kinase inhibitor fights millimolar cellular ATP — which is why cellular IC50 often sits far above the biochemical one.
  • Uncompetitive drugs get stronger where flux is highest, self-targeting overactive tissue. That selectivity is a design goal, not an accident.
  • kcat/Kmis the number to beat: it ranks substrates and caps at ~10⁸–10⁹ M⁻¹s⁻¹, the diffusion limit. An enzyme at that ceiling is "catalytically perfect" — it converts essentially every molecule it meets.

Current specificity constant

3.33 × 10⁶ M⁻¹s⁻¹ uninhibited

1.11 × 10⁶ M⁻¹s⁻¹ apparent