Parameter Reference

Complete reference for every parameter in Hedgehog’s YAML configuration files.

config.yml

The main configuration file. Controls input/output paths, parallelism, and references to all stage-specific configs.

config_mol_prep.yml

Preprocessing. Standardizes molecules before any descriptor computation. This stage aims to produce “clean” molecules by:

• removing salts and solvents and keeping the largest fragment
• disconnecting metals
• canonicalizing tautomers
• removing stereochemistry
• applying strict filters (allowed atom whitelist, no radicals, no isotopes, single fragment)

General Settings

config_descriptors.yml

Descriptors. Controls molecular descriptor calculation, filtering borders, and plotting options.

General Settings

The descriptors stage applies both layers together:

• borders define generic descriptor ranges such as molWt, logP, TPSA, hbd, hba, n_rings, and fsp3.
• structural_constraints are converted into additional upper bound checks on derived descriptor columns.

Use borders to shape broad property space and structural_constraints to cap specific motifs that can still pass those broad ranges.

Plotting Settings

config_structFilters.yml

Structural Filters. Controls structural alert screening and medicinal chemistry filters. Molecules flagged by enabled filters are removed from the pipeline.

General Settings

Structural Filter Profiles

The default structural filter configuration is the exploration profile in config_structFilters.yml. Three named ready-to-use profile files are shipped alongside it:

• config_structFilters_strict.yml - conservative profile for high-confidence hygiene screening
• config_structFilters_balanced.yml - practical mid-conservatism profile
• config_structFilters_exploration.yml - least conservative profile for retaining more chemistry diversity

config_synthesis.yml

Synthesis Feasibility. Controls the retrosynthesis feasibility stage, including synthesizability score thresholds.

config_docking.yml

Docking. Controls molecular docking using SMINA, GNINA, Matcha, or any explicit combination of them. Defines the receptor, search box, and engine-specific parameters.

General Settings

SMINA Configuration (smina_config)

GNINA Configuration (gnina_config)

Matcha Configuration (matcha_config)

When prepare_ligands is true, one input molecule may produce several prepared ligands. This can change row counts and downstream mapping. Keep it false for the default 1:1-oriented docking path unless you explicitly need an external preparation workflow.

config_docking_filters.yml

Three-Dimensional Filters. Post-docking 3D filters evaluate the quality of docked poses and remove poor candidates. Five independent filters can be combined with all (every filter must pass) or any (at least one must pass) aggregation.

General Settings

Aggregation

Deduplication

Docking can produce multiple poses per molecule when num_modes is greater than 1 (the default config uses num_modes: 1). After filtering, the pipeline deduplicates to unique molecules:

1. All passing poses are saved to filtered_poses.csv (full pose-level detail)
2. Poses are sorted by minimizedAffinity (best affinity first)
3. For each unique mol_idx, only the best-scoring pose is kept
4. Deduplicated molecules are saved to filtered_molecules.csv

SMILES for the output are taken from the original ligands.csv (2D SMILES) rather than regenerated from 3D coordinates, which preserves the original stereochemistry encoding.

config_weighted_score.yml

Controls the post-run Generator Reality Assessment used by HTML reporting and RUN_INFO.md.

The scorecard is explainable and intended to rank generator behavior, not to estimate hit probability. It also reports a secondary Final Candidate Pool Quality score for the survivor set.

General Settings

Component Weights (weights)

Weights are normalized over all configured components before scoring. When one component is unavailable, it is simply excluded, and the effective average is recomputed from the remaining available components.

physchem is measured from stages/02_descriptors_initial/filtered/pass_flags.csv as an all pass descriptor gate rate, so it reflects the early generated set rather than the final survivor pool. The mean flag pass rate is retained as evidence only. structural uses the stage survival rate from filtered and failed molecules, with the weakest structural filter as supporting evidence. Final descriptor files are used only as a fallback for older or partial runs. synthesis and docking_pose similarly prefer full stage evaluation artifacts before filtered or final survivor files.

Secondary Candidate Pool Weights (candidate_pool_weights)

candidate_pool_weights control the secondary Final Candidate Pool Quality score. It keeps the older survivor-pool interpretation: final-count yield saturation, mean descriptor flag pass rate, mean structural flag pass rate, and the same synthesis/docking/diversity formulas.

Yield and Structural Settings

Hard Caps (hard_caps)

Hard caps prevent a model from receiving a high generator score when an early AND-gate rejects most molecules.

Docking Thresholds (docking)

Increase strictness by moving bad_* upward and good_* downward, or relax by widening the interval.

Synthesis Thresholds (synthesis)

Raise or lower these to bias toward faster/easier synthetic routes.

config_moleval.yml

Controls generative evaluation metrics computed during report generation. These metrics assess diversity, scaffold coverage, and basic filter pass rates across pipeline stages.

General Settings

Metric Groups

Each flag enables or disables a group of related metrics.