Tutorial B.2 — Protein synthesis on a coarse-grained ribosome

Goal: synthesize a protein residue by residue on TOPO’s own coarse-grained ribosome, using codon-resolved kinetics with topo-csp. This is the ribosome-based counterpart to Tutorial B.1, which replaces the physical ribosome with an analytic cylindrical tunnel.

Everything here is standalone TOPO: the ribosome is a truncated CG bead model (ribosome_trunc.pdb, loaded by topo.csp.ribosome.load_ribosome) — no external .cor/.psf/.prm files. The nascent chain grows N→C through the exit region and is ejected once complete.

Synthesis on the ribosome — the chain (coloured beads) grows through TOPO’s coarse-grained ribosome (translucent grey); already-emerged N-terminal residues fold while the C-terminus is still being added inside.

The GIF is for the 4c5c/ system. After a run, view your own synthesis in VMD: stitch the per-length frames into one movie (adding the ribosome as scenery), then launch VMD from inside synth_out/ (the generated movie.tcl loads movie.{psf,dcd} by basename, so it only resolves from that folder):

topo-csp-movie -o synth_out --ribosome ribosome_trunc.pdb   # -> synth_out/movie.{psf,dcd,tcl}
cd synth_out && vmd -e movie.tcl

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

Prerequisite: the coarse-grained model of Tutorial A.1 and the domain-scaling idea of Tutorial A.2.

Two worked systems

System	Residues	Notes
4c5c/	306, multidomain	Full-length synthesis L = 1 → 306, then ejection. The main validation case.
P0CX28/	106, single-domain	The single-domain protein from Tutorial A.1, L = 1 → 106, nscale = 2.5044.

Files (per system)

File	Role
*_clean.pdb	Target folded structure (defines the native contacts).
*_stride.dat	Precomputed STRIDE backbone hydrogen bonds.
domain.yaml	Domain definition / contact nscale (see Domain definition file).
*_mrna.txt	The mRNA codon sequence that times each residue.
trans_times.txt	Per-codon translation times (kinetics input).
ribosome_trunc.pdb	TOPO’s coarse-grained truncated ribosome.
csp_val.ini	Full-length run config (L0=1 → L_max, AllBonds, equilibrium-PTC, ejection).
csp_debug.ini	Short clamped debug profile (4c5c only).

Run it

From a system folder (e.g. 4c5c/):

topo-csp -f csp_val.ini        # -> synth_out/

The runner uses codon-resolved kinetics (each elongation cycle split into three kinetic sub-stages) with a per-stage dt-halving stability guard, rigid AllBonds (the default), and always-on equilibrium-PTC seeding — each new residue is placed one peptide bond from the previous C-terminus, clear of the ribosome, so rigid bonds seed cleanly. A successful full-length run shows no [stability] lines in the log.

What it produces

• synth_out/L_001/ … L_<L_max>/ — one folder per chain length, each with the MD trajectory and the nascent structure at that length.

• synth_out/ejection/ — the post-synthesis release: traj_final.pdb, the built-once native-contact PDB, and run metadata.

Validating the run

A successful run leaves no [stability] lines in the log (per-stage potential energy stayed finite throughout), and synth_out/ejection/traj_final.pdb shows the released chain clear of the tunnel — not penetrating the ribosome.