Tutorial B.1 — Protein synthesis through an analytic exit tunnel¶

This is the structure-based (topo) twin of cosmo’s tutorial 09. The ribosome-based runner (Tutorial B.2) builds the ribosome from explicit beads and threads the nascent chain through the coarse-grained exit tunnel. Here the tunnel is modelled analytically instead: a cylindrical bore of radius r along the X-axis drilled through an infinite wall at x_exit (a “hole in an infinite wall”). There are no ribosome beads — the System is the nascent chain only, so it is fast and never jams.

The chain is a folded protein built with topo’s structure-based Gō contacts, so it can fold co-translationally as it extrudes and once it clears the bore.

full protein synthesis and ejection through the tunnel

Protein synthesis → ejection. The chain (N→C rainbow beads) grows from the PTC (C-terminus, red) and extrudes N-terminus-first down the transparent blue bore (with the red closed PTC cap and the translucent grey exit-face wall), emerges past the wall, and folds into the ejected protein just outside the tunnel.

The cylinder ribosome model (`topo.csp.cylinder`)¶

The analytic tunnel is a different physics of confinement than the explicit-bead ribosome, so it lives in the package as a parallel module to the explicit-bead runner (topo.csp.protocol): topo.csp.cylinder, driven by the topo-cylinder console command. It reuses the package’s tested, unchanged low-level machinery from topo.csp.core (the one-time contact precompute, the build-once-subset length model, the seed / restrain / output path) and adds only the one new force, add_tunnel_cylinder, plus its own nascent-only synthesis loop.

Timing is the same O’Brien codon kinetics as topo-csp — each residue’s MD length comes from its codon dwell time (mrna + scale_factor) via topo.csp.kinetics. The only difference from the explicit protocol is that the cylinder runs a single MD segment per residue (there is no A→P translocation to split into three sub-stages).

The model (forbidden region `S`)¶

   d                              (cytosol: free, any d)
   ^   |##### solid ribosome S #####|
 r |···|············ bore ··········|··············>  allowed past exit
   +---|----------------------------|----------------> x
     x_lo (PTC)                  x_exit
       |##### solid ribosome S #####|
                              ^ infinite exit-face wall (d > r)

A bead is penalised by its penetration depth into S (everything outside the bore up to the exit face, plus the closed PTC end), escaping via whichever face is nearer — the bore wall (radial inward push → keeps the chain extended) or the exit face (+x push → a cytosol bead can re-enter the tunnel only through the bore). The 90° mouth corner is rounded by a fillet (radius rho) so the potential is continuous and the MD is stable. The C-terminus is seeded and position-restrained on the tunnel axis at the PTC (x_lo, 0, 0); new residues are seeded there.

Run¶

cd tutorials/B1_translation_cylinder
topo-cylinder -f cylinder.ini          # or: python -m topo.csp.cylinder -f cylinder.ini

All parameters live in cylinder.ini. The nascent chain is the 106-residue P0CX28, with domain.yaml + the precomputed STRIDE for the contact map, and P0CX28_mrna.txt for the codon kinetics. Tunnel defaults: bore radius 0.9 nm, length 10.0 nm (x_lo=0, x_exit=10), axis on X, mouth fillet 0.2 nm, wall stiffness 8368 kJ/mol/nm². The kinetics keys (mrna, scale_factor, time_stage_1/2, max_steps_per_stage) are the same as the CSP tutorials; the demo caps each residue at 2000 steps (delete the clamps for production).

Post-synthesis: ejection¶

Once the chain reaches its final length, an optional post-synthesis free run continues the same system from the finished structure — the same ejection_steps key as topo-csp. The phase releases the C-terminus restraint, so the completed protein is free to diffuse; the analytic tunnel stays on (bore + closed PTC end + exit wall), so the only way out is +x through the exit. This tests whether the nascent protein diffuses out of the tunnel and folds in the cytosol.

ejection (ejection_steps) — the free run, written to <outdir>/ejection/.

ejection_steps     = 300_000   # use a LONG run so the protein can clear the tunnel

Visualize / validate¶

Stitch the per-length trajectories into one movie and draw the analytic tunnel (bore tube, closed PTC cap, and the infinite exit-face wall as an annulus whose hole is the bore), reading the geometry from the same cylinder.ini. Two equivalent ways:

# Module (preferred): the shared stitcher with a --tunnel flag.
topo-csp-movie -o synth_out --tunnel cylinder.ini      # or: python -m topo.csp.movie -o synth_out --tunnel cylinder.ini
cd synth_out && vmd -e movie.tcl                       # movie.tcl loads movie.{psf,dcd} by name -> run it from synth_out/

# In-folder script (equivalent; self-contained convenience wrapper).
python make_movie_cylinder.py -o synth_out -f cylinder.ini
cd synth_out && vmd -e movie.tcl                       # run from synth_out/ so movie.{psf,dcd} resolve

Both draw the same tunnel from the same topo.csp.cylinder.tunnel_tcl geometry (--wall-outer NM sets the drawn exit-wall radius; default bore radius + 3 nm). You then see the chain thread the (blue, transparent) bore, the red PTC end cap it grows away from, and the grey exit wall it emerges through — then fold once it clears the tunnel. (Plain topo-csp-movie -o synth_out, with no --tunnel, also works — it just omits the tunnel.)

For the full movie reference (both synthesis models, all topo-csp-movie options), see Visualizing the synthesis process.