Protein synthesis: overview

TOPO can grow a protein vectorially, N-terminus first, out of a ribosome while the nascent chain folds as it emerges — reproducing co-translational folding under codon-resolved kinetics. This page is the map: the biology being modelled, the two ribosome models TOPO offers, and which to use. The detailed references are linked at the end.

The biology in one minute

A ribosome synthesizes a protein one residue at a time, N→C, threading the growing (“nascent”) chain out through the ~80 Å exit tunnel, where it begins to fold before the full sequence exists. How long the ribosome dwells on each codon sets how much time each segment has to sample conformations before the next residue arrives; slow (rare) codons act as translational pauses that can change folding outcomes.

Each residue is added through one elongation cycle — (1) codon-dependent aminoacyl-tRNA decoding at the A site (usually rate-limiting), (2) peptidyl transfer at the peptidyl-transferase centre (PTC), (3) translocation (A→P→E). TOPO times each residue from its mRNA codon and, in the explicit model, splits the cycle into these three sub-stages.

Two ribosome models

Both grow the same structure-based (Gō-like) Cα nascent chain — see The TOPO model: theory and force field for the base force field — and both use the same codon kinetics. They differ only in how the exit tunnel is represented:

Explicit CG ribosome

Analytic cylinder

Runner

topo-csp (Synthesis in coarse-grained ribosome model)

topo-cylinder (Synthesis in cylinder ribosome model)

Tunnel

a real truncated, coarse-grained large subunit (~4,600 rigid beads)

an analytic cylindrical bore through an infinite wall

Interactions

ribosome↔nascent excluded volume + electrostatics; tRNA tether; A→P translocation

geometric confinement only

Needs a structure?

yes — a ribosome_trunc.pdb (The ribosome structure (get one, or build your own))

no

Per residue

three MD sub-stages (transfer / translocation / wait)

one MD segment

Cost / robustness

heavier; realistic tunnel wall

fast; never jams

Which to use

  • Cylinder — for fast exploration of how tunnel geometry + codon kinetics shape folding, or when you have no ribosome structure. Simplest starting point.

  • Explicit — when the tunnel-wall charge, tunnel shape (constriction site / vestibule), or translocation-coupled forces matter to your question.

Warning

The two models are comparable only in the mean per-residue dwell time, not in confinement chemistry. The cylinder omits the ribosome’s electrostatics and surface excluded volume and has a uniform straight bore. Do not compare folding observables (folding order, Q-vs-length, radius of gyration) across the two models without accounting for those missing terms. See Synthesis in cylinder ribosome model §”Physical scope”.

Where to go next