tRNA Proofreading — Free-Energy Landscape

tRNA Pool

Cognate : near-cognate ratio 1 : 5

Proofreading stringency 1.0×

Simulation speed 1.0×

Elongation Cycle

Sampling — testing incoming aminoacyl-tRNA against the free-energy landscape…

Elongation rate

0.0 aa/s

Codons made

Error rate

0 / 10⁴

Last dwell time

—

How it works

This is the same two-step Hopfield/Ninio kinetic-proofreading cycle as the 3D ribosome scene, but drawn as what biochemists actually plot: a free-energy reaction-coordinate diagram. Each candidate tRNA is a ball rolling across a landscape with two barriers (transition states); it is stochastically kicked forward or backward at each barrier by an exponential race between the same forward/reverse rate constants:

Height of every well/barrier is reconstructed from the rate
constants themselves via Eyring transition-state theory:
  k = A * exp(-ΔG‡/kT)  =>  ΔG‡ = kT * ln(A/k)

Step 1 (before GTP hydrolysis):  correct pairing -> shallow uphill, deep intermediate well
                                  mismatch        -> steep uphill, shallow/unstable intermediate
Step 2 (proofreading, after hydrolysis): correct -> low second barrier, deep final well
                                          mismatch -> high second barrier (raised by stringency)

Overall discrimination:  D = D1 x D2   (independent checks multiply)

Because the cognate curve's intermediate sits in a real energy well while the near-cognate curve's intermediate is uphill of the free state, a mismatched tRNA is thermodynamically pulled back off the landscape at both checkpoints — this is why kinetic proofreading works even though a single equilibrium binding step could never separate cognate from near-cognate this cleanly. The scrolling strip below the landscape is a live fidelity timeline: every accepted codon is plotted as a dot, green for correct and red for a misincorporation, exactly as they happen in simulated time.

Cognate : near-cognate ratio — relative concentration of matching vs. mismatching tRNAs competing to reach the landscape (rare codons mean fewer cognate attempts before a near-cognate one gets tested).
Proofreading stringency — scales the height of the second barrier for a near-cognate tRNA that slipped past step 1.
Common / Rare codon — switches the current codon's cognate-tRNA abundance for the next cycle.

Cognate landscape / accepted Near-cognate landscape / misincorporated Candidate (ball on curve)

Events