opt

Optimizes a single layered enzyme PDB (or XYZ + --ref-pdb) to a local minimum using the ML/MM calculator (MLIP region + movable MM shell + frozen outer environment). Use it to relax a full-system layered structure. --opt-mode grad (default) runs L-BFGS, --opt-mode hess runs RFOptimizer (RFO), --flatten flattens imaginary modes after optimization, and --mm-only minimizes the full system on the MM force field only, skipping the MLIP component (grad/L-BFGS only; microiteration auto-disabled). Microiteration (--microiter, default on) relaxes the movable-MM shell in hess mode.

Examples

Command form:

mlmm opt -i INPUT --parm PARM7 --model-pdb ML_REGION -q CHARGE [options]

mlmm opt --help shows core options; mlmm opt --help-advanced shows the full option list.

Minimal L-BFGS optimization (grad mode, default):

# Minimal L-BFGS optimization (grad mode, default)
mlmm opt -i pocket.pdb --parm real.parm7 --model-pdb ml_region.pdb \
 -q 0 --out-dir ./result_opt

Tighten convergence and keep an optimization trajectory:

# Tighten convergence and keep an optimization trajectory
mlmm opt -i pocket.pdb --parm real.parm7 --model-pdb ml_region.pdb \
 -q 0 --thresh gau_tight --dump --out-dir ./result_opt_tight
# add one harmonic distance restraint: --dist-freeze "[(12,45,2.20)]" --bias-k 20.0

Switch to heavy mode (RFO):

# Switch to heavy mode (RFO)
mlmm opt -i pocket.pdb --parm real.parm7 --model-pdb ml_region.pdb \
 -q 0 --opt-mode hess --out-dir ./result_opt_rfo
# use the ORB backend instead of the default: --backend orb

Workflow

1. Input handling – The tool accepts -i/--input as a PDB or XYZ file (use --ref-pdb with XYZ inputs). The optimizer reads coordinates from this PDB via pysisyphus.helpers.geom_loader. ML/MM layer definitions come from --model-pdb, --model-indices, or --detect-layer (B-factor encoding: B=0 ML, B=10 Movable-MM, B=20 Frozen).

2. ML/MM calculator setup – Build the ML/MM calculator (MLIP backend + hessian_ff). The -b/--backend option selects the MLIP (uma, orb, mace, or aimnet2; default uma). --parm provides Amber MM topology; --model-pdb defines the ML region. When --embedcharge is enabled, xTB point-charge embedding is applied to correct for MM-to-ML environmental electrostatic effects.

3. Optimization – The optimizer runs in the selected --opt-mode (grad = L-BFGS, hess = RFOptimizer); see the CLI options table for the accepted aliases.

   • --flatten enables post-optimization flattening of imaginary modes. All detected imaginary modes are flattened each iteration until none remain or the internal loop cap is reached.

4. Restraints – Optional harmonic distance restraints via --dist-freeze / --bias-k (see CLI options).

5. Dumping & conversion – --dump writes optimization_trj.xyz; when conversion is enabled, trajectories are mirrored to .pdb for PDB inputs (with B-factor annotations). opt.dump_restart can emit restart YAML snapshots.

6. Exit codes – 0 success, 2 zero step (step norm < min_step_norm), 3 optimizer failure, 130 keyboard interrupt, 1 unexpected error.

Outputs

out_dir/ (default: ./result_opt/)
├─ final_geometry.xyz          # Always written
├─ final_geometry.pdb          # Only when the input was a PDB and conversion is enabled (B-factors annotated)
├─ optimization_trj.xyz        # Only if dumping is enabled
├─ optimization.pdb            # PDB conversion of the trajectory (PDB inputs, conversion enabled)
├─ optimization_all_trj.xyz    # Concatenated full trajectory (when --dump)
├─ optimization_all.pdb        # PDB companion of the full trajectory (PDB inputs, when --dump)
└─ restart_*.yaml              # Optional restarts when opt.dump_restart is set

Console output prints resolved configuration blocks (geom, calc, opt, lbfgs), progress every print_every cycles, and a final wall-clock time summary.

CLI options

The full flag list is in the generated command reference; the table below covers the options that need explanation. Default values shown are used when the option is not specified.

Option	Description	Default
-i, --input PATH	Input structure accepted by geom_loader (.pdb, .xyz, _trj.xyz).	Required
--ref-pdb PATH	Reference PDB topology when input is XYZ.	None
--parm PATH	Amber parm7 topology for the full enzyme.	Required
--model-pdb PATH	PDB defining the ML region atoms. Optional when --detect-layer is enabled.	None
--model-indices TEXT	Comma-separated atom indices for the ML region (ranges allowed, e.g. 1-5). Alternative to --model-pdb.	None
--model-indices-one-based / --model-indices-zero-based	Index convention for --model-indices.	1-based
--detect-layer / --no-detect-layer	Auto-detect ML/MM layers from B-factors (B=0 ML, B=10 Movable-MM, B=20 Frozen).	Enabled
-q, --charge INT	Charge of the ML region.	None (required unless -l is given)
-l, --ligand-charge TEXT	Per-resname charge mapping (e.g., GPP:-3,SAM:1). Derives net charge when -q is omitted. Requires PDB input or --ref-pdb.	None
-m, --multiplicity INT	Spin multiplicity (2S+1).	1
--freeze-atoms TEXT	Comma-separated 1-based indices to freeze.	None
--radius-freeze FLOAT	Distance cutoff (Å) from ML region for movable MM atoms. Atoms beyond this are frozen. Providing this disables --detect-layer. Alias: --movable-cutoff.	None
--radius-partial-hessian, --hess-cutoff FLOAT	Distance cutoff (Å) from ML region for MM atoms included in Hessian calculation. Combinable with --detect-layer.	None
--mm-backend [hessian_ff|openmm]	MM backend (analytical Hessian vs OpenMM finite-difference).	hessian_ff
--mm-only / --no-mm-only	Skip the MLIP component and minimize on the MM force field only. Layers are still honored via B-factor / --radius-freeze; only --opt-mode grad is supported in this mode and microiteration is disabled automatically. Suited to fast MM pre-relaxation before ML/MM ONIOM optimization.	False
--link-atom-method [scaled|fixed]	Link-atom placement: scaled ($g$-factor) or fixed 1.09/1.01 Å.	scaled
--out-json/--no-out-json	Write machine-readable result.json to out_dir.	False
--dist-freeze TEXT	Python-literal (i, j, target_A) tuples for harmonic restraints (inline literal or YAML/JSON file path); omit target_A to restrain the starting distance.	None
--one-based / --zero-based	Index convention for --dist-freeze.	1-based
--bias-k FLOAT	Harmonic bias strength (eV/Ų).	300.0
--max-cycles INT	Hard limit on optimization iterations.	10000
--opt-mode [grad|hess|light|heavy|lbfgs|rfo]	Optimizer mode: grad (LBFGS) or hess (RFO). Aliases light/heavy and lbfgs/rfo accepted.	grad
--microiter/--no-microiter	Microiteration: alternate ML 1-step (RFO) + MM relaxation (LBFGS). Only effective in hess mode (no-op in --opt-mode grad).	True
--flatten/--no-flatten	Enable/disable the post-optimization imaginary-mode flatten loop.	False
--dump/--no-dump	Emit trajectory dumps (optimization_trj.xyz, optimization_all_trj.xyz).	False
--convert-files/--no-convert-files	Enable or disable XYZ/TRJ to PDB companions for PDB inputs.	True
-o, --out-dir TEXT	Output directory for all files.	./result_opt/
--thresh TEXT	Override convergence preset (gau_loose, gau, gau_tight, gau_vtight, baker, never).	None (gau applied internally)
--config FILE	Base YAML configuration file.	None
--show-config/--no-show-config	Print resolved YAML layer information before execution.	False
-b, --backend CHOICE	MLIP backend for the ML region: uma, orb, mace, aimnet2.	uma
--embedcharge/--no-embedcharge	Enable xTB point-charge embedding correction for MM-to-ML environmental effects (experimental).	False
--embedcharge-cutoff FLOAT	Cutoff radius (Å) for embed-charge MM atoms.	12.0
--cmap/--no-cmap	Enable CMAP (backbone cross-map dihedral correction) in model parm7. Default: disabled (consistent with Gaussian ONIOM).	--no-cmap
--dry-run/--no-dry-run	Validate options and print execution plan without running optimization. Shown in --help-advanced.	False

Convergence threshold presets

Forces in Hartree/bohr, steps in bohr.

Preset	Purpose	max|F|	RMS(F)	max|step|	RMS(step)
gau_loose	Loose/quick pre-optimization; rough path searches	2.5e-3	1.7e-3	1.0e-2	6.7e-3
gau	Standard Gaussian-like tightness for routine work	4.5e-4	3.0e-4	1.8e-3	1.2e-3
gau_tight	Tighter; better structures / freq / TS refinement	1.5e-5	1.0e-5	6.0e-5	4.0e-5
gau_vtight	Very tight; benchmarking/high-precision final structures	2.0e-6	1.0e-6	6.0e-6	4.0e-6
baker	Baker-style rule (converged only when all four force/step values below are met and |dE| < 1e-6)	3.0e-4	2.0e-4	3.0e-4	2.0e-4

YAML configuration

Settings are applied with defaults < config < explicit CLI < override. The accepted sections are geom (coord_type, freeze_atoms), calc / mlmm (ML/MM calculator: backends, devices, Hessian mode, embedding), opt (shared optimizer controls), and the optimizer-specific lbfgs / rfo sections.

geom:
 coord_type: cart               # cartesian vs dlc internals (dlc needs --opt-mode hess; grad/L-BFGS falls back to cart)
 freeze_atoms: []               # 1-based frozen atoms
calc:
 charge: 0                      # net charge
 spin: 1                        # spin multiplicity 2S+1
mlmm:
 real_parm7: real.parm7         # Amber parm7 topology
 model_pdb: ml_region.pdb       # ML region definition
 backend: uma                   # uma | orb | mace | aimnet2
 hessian_calc_mode: Analytical  # or FiniteDifference
opt:
 thresh: gau                    # convergence preset
 max_cycles: 10000              # optimizer cycle cap
 out_dir: ./result_opt/         # output directory

microiter

Used only when --microiter is active with --opt-mode hess. micro_thresh sets the L-BFGS convergence preset for the MM relaxation step. When null or omitted, the micro step uses the same preset as the macro optimizer (--thresh / opt.thresh). There is no --micro-thresh CLI flag; set this in YAML.

Full schema (every section, key, and default): YAML Reference.

See Also

• Common Error Recipes — Symptom-first failure routing

• Troubleshooting — Detailed troubleshooting guide

• tsopt — Optimize transition states (saddle points) instead of minima

• freq — Vibrational analysis to confirm a minimum was reached

• all — End-to-end workflow that pre-optimizes endpoints

• YAML Reference — Full opt, lbfgs, rfo configuration options

• Glossary — Definitions of L-BFGS, RFO