Synthesis control options

Continuous-synthesis (co-translational) runs are configured from a separate .ini control file (e.g. csp.ini), read by cosmo.csp.protocol.read_csp_config(), which returns a CSPConfig (inputs, length schedule, and a populated RunParams). This is the synthesis analogue of the single-chain Simulation control options page: the same [OPTIONS] / key = value grammar, a different set of options.

• Comments: inline or on their own line, starting with ; or #.

• Keyword and value are separated by = or :.

• Every option below has a default except the ones marked required.

• Units are OpenMM defaults — nm, ps, kJ/mol, K, kJ/mol/nm² — and dwell times are in seconds. Integers may use _ digit separators (200_000).

For the physics behind these knobs (the three-stage elongation cycle, the codon-resolved kinetics, the O’Brien 12-10-6 ribosome wall), see Synthesis on a coarse-grained ribosome. This page is the parameter reference.

Running a synthesis

The runner lives in the package as cosmo.csp. Once cosmo is installed (pip install -e . from the repo root) either of these works:

cosmo-csp -f csp.ini              # installed console command
python -m cosmo.csp -f csp.ini    # module form

# stitch the per-stage trajectories into one VMD movie afterwards
cosmo-csp-movie -o synth_out --ribosome 4v9d_50S_PtR_5jte_AtR_model_cg_trunc.pdb

A GPU is recommended: the truncated ribosome adds several thousand rigid beads.

Example csp.ini:

[OPTIONS]
; --- inputs (pdb_file, ribosome are required) ---
pdb_file = asyn.pdb              ; full native PDB; the CG model is built from it
ribosome = 4v9d_50S_PtR_5jte_AtR_model_cg_trunc.pdb   ; truncated CG ribosome (P-/A-anchors + rigid scenery)
model    = hps_urry              ; nascent IDP force field (any model works; hps_kr is the default)

; --- length schedule ---
L0    = 5            ; first nascent length (default 1)
L_max = 8            ; final nascent length (default: full residue count)

; --- codon-resolved kinetics ---
mrna         = mrna.txt        ; one codon per residue (required for per-codon timing);
                               ; or "fastest"/"slowest"/"median" to auto-build a synonymous-codon mRNA
codon_times  = trans_times.txt ; table path = per-codon (required, no bundled default);
                               ; a positive number of s = uniform instead
scale_factor = 4331293         ; in-vivo seconds -> in-silico ns compression (larger = faster)
time_stage_1 = 0.000340        ; mean peptidyl-transfer dwell (s)
time_stage_2 = 0.004201        ; mean translocation dwell (s)
random_seed  = 1               ; reproducible first-passage-time schedule

; --- test clamps (leave UNSET in production; see the warning below) ---
max_steps_per_stage = 40
min_steps_per_stage = 20

; --- integrator / output ---
dt     = 0.01        ; timestep (ps)
ref_t  = 300         ; temperature (K)
tau_t  = 0.01        ; Langevin friction (1/ps)
nstout = 20          ; trajectory/log output interval (steps)

; --- ribosome / PTC mechanics ---
; PTC geometry is always optimized (A/P targets one peptide bond, ~0.38 nm,
; the selected model's bond length, apart and EV-clear) -- no knob. Bonds default
; to flexible (constraints = None;
; set constraints = AllBonds for rigid bonds).
restraint_k = 83680  ; C-terminus harmonic restraint (kJ/mol/nm^2)
minimize    = yes    ; energy-minimize each seeded structure before its MD
; tunnel_wall = yes  ; one-sided tunnel floor (default on; plane auto-derived)

; --- post-synthesis phases (steps; 0 = skip) ---
ejection_steps     = 20000   ; release the restraint; chain diffuses out (+x)
dissociation_steps = 0       ; free run away from the ribosome

; --- hardware / output ---
device = GPU
ppn    = 4
outdir = synth_out

Parameter summary

“Required = yes” means the run cannot proceed without it. — in the Default column means there is no default. Options are grouped by role; they all live in the same single [OPTIONS] section.

Inputs & length schedule

Option	Type	Required	Default	Description
pdb_file	str	yes	—	Full native PDB of the target protein. cosmo builds the one-bead-per-residue CG model from it; the nascent chain at length L uses residues 1..L.
ribosome	str	yes	—	Truncated CG ribosome PDB. Source of the P-/A-anchors and the rigid (mass-0) scenery. Supplying it is the signal to load it as rigid — there is no rigid_ribosome key. Must carry the tRNA beads under the expected names (segids PtR/AtR, resid 76, beads R/P/BR2).
model	str	no	hps_kr	Nascent IDP force field. Any model works (hps_kr / hps_urry / mpipi); hps_kr is merely the default. The ribosome↔nascent 12-10-6 excluded volume uses the model-independent O’Brien Rmin/2 collision radii (standalone OBRIEN_RMIN_2_NM / OBRIEN_RNA_RMIN_2_BEADS tables in cosmo.parameters.model_parameters), decoupled from the force field; the nascent IDP↔IDP interaction is whatever the selected model provides (Ashbaugh–Hatch or Wang–Frenkel).
mrna	str	for per-codon timing	—	mRNA sequence file (raw nucleotides; one codon per residue plus one stop), or the keyword fastest / slowest / median to auto-build a synonymous-codon mRNA (each residue’s fastest/slowest/median-dwell-time codon per the codon_times table, written next to the PDB). Required unless codon_times is a number (uniform timing). A real filename must not be fastest/slowest/median.
codon_times	str or float	for per-codon timing	—	Codon-timing key. A path to a CODON  seconds  amino_acid table = per-codon timing (required, no bundled default – pick one under assets/csp/codon_dwell_times/); a positive number of seconds = uniform timing (no mrna needed). A table filename must not be a bare number.
L0	int	no	1	First nascent length to synthesize.
L_max	int	no	full length	Final nascent length. Must satisfy 1 <= L0 <= L_max <= N_full.
outdir	str	no	synth_out	Output root; each residue writes L_<L>/stage_<1,2,3>/ beneath it.

Note

There is no domain_def, stride_output_file, or nascent_ev_radii option: those are topo’s Gō-model inputs. cosmo’s chain is sequence-based, so a length-L model is just buildCoarseGrainModel on residues 1..L — no STRIDE, no native-contact map.

Kinetics & schedule length

Option	Type	Required	Default	Description
scale_factor	float	no	4331293	In-vivo-seconds → in-silico-ns compression (t_sim_ns = t_s · 1e9 / scale_factor). Larger ⇒ fewer MD steps per residue ⇒ faster, while preserving the relative fast/slow-codon timing.
time_stage_1	float [s]	no	0.00034	Mean peptidyl-transfer dwell. The per-residue dwell is an exponential draw with this mean.
time_stage_2	float [s]	no	0.004201	Mean translocation dwell. Stage 3’s mean is the remainder τ(next codon) − time_stage_1 − time_stage_2.
random_seed	int	no	— (nondet.)	Seed for the first-passage-time sampler (reproducible dwell schedule).
ribosome_traffic	bool	no	no	Apply the ribosome-traffic (polysome) dwell-time correction, if available, on top of the per-codon kinetics. Off by default (single-ribosome timing).
initiation_rate	float	no	0.083333	Translation initiation rate (1/s). Consumed only when ribosome_traffic = yes.
max_steps_per_stage	int	no	— (uncapped)	Testing only. Upper clamp on each stage’s MD step count. Breaks the physical timescale mapping — leave unset in production.
min_steps_per_stage	int	no	1	Testing only. Lower clamp on each stage’s MD step count.
ejection_steps	int	no	0	Post-synthesis ejection phase (steps); 0 = skip. Releases the C-terminus restraint so the chain diffuses out (+x).
dissociation_steps	int	no	0	Post-synthesis dissociation phase (steps); 0 = skip. A further free run away from the ribosome.

Warning

``max_steps_per_stage`` / ``min_steps_per_stage`` are testing-only knobs. They clamp the MD step count so examples finish quickly, which breaks the physical timescale mapping. In production leave them unset so step counts come entirely from the kinetics (scale_factor, the codon times, dt). The sampled dwell times in seconds are always written to dwell_times.dat.

Integrator, ribosome & PTC mechanics

These configure the shared per-length engine (RunParams, consumed by run_length()).

Option	Type	Default	Description
dt	float [ps]	0.01	Integration timestep. (cosmo uses flexible harmonic bonds and soft HPS/mpipi potentials — there is no rigid-bond / dt-halving stability guard.)
ref_t	float [K]	300	Langevin temperature.
tau_t	float [ps⁻¹]	0.01	Langevin friction coefficient.
nstout	int	50	Trajectory (DCD) and log output interval, in steps, for every stage.
constraints	str	None	Bond treatment: None (flexible harmonic bonds, the default) or AllBonds (rigid distance constraints). Both are supported. None is the default because backbone flexibility is physically meaningful for intrinsically disordered chains; AllBonds pins every CA/P bond at its equilibrium length, removing the fast bond-stretch mode so a larger timestep can be used. Constraints act only on the pseudo-bonds — the non-bonded potentials (Ashbaugh-Hatch / Wang-Frenkel and, with a ribosome, the 12-10-6 excluded volume) are unaffected, so AllBonds does not by itself prevent a stiff-EV blow-up (the per-stage dt-halving guard handles that).
restraint_k	float [kJ/mol/nm²]	83680	Stiffness of the C-terminus harmonic position restraint to the A/P target point (= 200 kcal/mol/Ų). Switching the target A→P is how translocation is reproduced. (Its k is a per-particle parameter so it coexists with the tunnel wall’s global k.)
minimize	bool	yes	Energy-minimize each seeded structure before running that stage’s MD.
tunnel_wall	bool	yes	Apply the one-sided half-harmonic tunnel wall (a floor below the synthesis point). The plane x₀ is auto-derived from the ribosome (min(A-target.x, P-target.x)) and the stiffness is a fixed model constant — neither is a key; only this on/off toggle.
device	str	CPU	Compute platform: CPU or GPU (CUDA). A GPU is recommended given the rigid-ribosome bead count.
ppn	int	1	Number of CPU threads (device = CPU).

Note

Boolean options accept yes/no, true/false, 1/0. The trna_tether field exists on RunParams but is forced off by the CSP runner — CSP needs the switchable A↔P position restraint, so the O’Brien tRNA tether (which targets only the P-site) is incompatible with the 3-stage translocation.

Notes on individual options

Required inputs (pdb_file / ribosome)

A synthesis run cannot start without both. pdb_file supplies the sequence (the length-L model is buildCoarseGrainModel on residues 1..L — no STRIDE, no contact map). ribosome is the truncated CG ribosome providing the P-/A-anchors and the rigid scenery; it must carry tRNA beads under the fixed names (segids PtR/AtR, resid 76, beads R/P/BR2) or anchor lookup — and the always-on PTC-geometry optimization — fail.

Per-codon vs. uniform timing (mrna / codon_times)

codon_times selects the timing mode by its value type: a path → per-codon timing (mrna required); a positive number of seconds → uniform timing (no mrna). There is no bundled default — per-codon timing needs an explicit table path (pick one under assets/csp/codon_dwell_times/). A codon-time table filename must not be a bare number. Setting mrna = fastest, slowest or median auto-builds a synonymous-codon mRNA from the protein + table (see Codon dwell-time tables (per-codon timing)).

Ribosome ↔ nascent excluded volume

The rigid ribosome interacts with the chain via the O’Brien 12-10-6 excluded volume (sum combining rule R = Rmin/2ᵢ + Rmin/2ⱼ, ε = 0.000132 kcal/mol) plus Debye–Hückel (Yukawa) electrostatics. The per-bead Rmin/2 values are inherited from topo and are model-independent steric radii: they live in the standalone OBRIEN_RMIN_2_NM (per-AA) and OBRIEN_RNA_RMIN_2_BEADS (rRNA P/R/BR) tables in cosmo.parameters.model_parameters, decoupled from any force field, so the excluded volume is identical for every nascent model.

Post-synthesis phases (ejection_steps / dissociation_steps)

After the last residue, ejection_steps > 0 runs a phase with the C-terminus restraint released (rigid ribosome and tunnel wall still present), so the finished chain diffuses out of the tunnel. dissociation_steps > 0 continues the free protein away from the ribosome. Both write their own output folders.

Output layout and progress log

Every stage writes a standalone, nascent-only trajectory to <outdir>/L_<L>/stage_<s>/. A per-residue <outdir>/dwell_times.dat records the codon and the three sampled dwell times (seconds, ns, MD steps). Stitch the per-stage trajectories into one VMD movie with cosmo-csp-movie -o <outdir> --ribosome <ribosome>.pdb. Set COSMO_CSP_VERBOSE=1 for the full per-stage banners. See Synthesis on a coarse-grained ribosome for the output tree.