Protein synthesis: overview

cosmo can grow a chain vectorially, N-terminus first, out of a ribosome while the nascent chain samples its conformations as it emerges — reproducing co-translational synthesis of an intrinsically disordered protein under codon-resolved kinetics. This page is the map: the biology being modelled, the two ribosome models cosmo 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 sample conformations before the full sequence exists. How long the ribosome dwells on each codon sets how much time each segment has to explore before the next residue arrives; slow (rare) codons act as translational pauses that can change the emerging ensemble. For a disordered chain the readout is not a native fold but the conformational statistics — compaction, extension, contacts — of the chain as it extrudes.

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). cosmo 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 sequence-based IDP (HPS / mpipi) one-bead-per-residue (Cα) nascent chain — the same force field cosmo uses for equilibrium runs, see Tutorial 2 — Models & force fields — and both use the same codon kinetics. They differ only in how the exit tunnel is represented:

Explicit CG ribosome

Analytic cylinder

Runner

cosmo-csp (Synthesis on a coarse-grained ribosome)

cosmo-cylinder (Synthesis through an analytic tunnel (cylinder model))

Tunnel

a real truncated, coarse-grained large subunit (~4,600 rigid beads; E. coli 4V9D)

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 truncated CG ribosome 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

Both add optional post-synthesis phases once the chain reaches full length, run in order: a stall hold at the PTC (restraint still on) then an ejection free run (restraint released) — see Synthesis control options.

Which to use

  • Cylinder — for fast exploration of how tunnel geometry + codon kinetics shape the disordered ensemble as it extrudes, 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 conformational observables (contact patterns, compaction-vs-length, radius of gyration) across the two models without accounting for those missing terms. See Synthesis through an analytic tunnel (cylinder model) §”The model: analytic exit tunnel”.

Where to go next