Dynamic Polymer Generation

This guide explains how to generate polymer chains on-the-fly from raw monomer SMILES strings, eliminating the need for pre-built polymer SDF files.

Overview

PolyzyMD supports two modes for polymer generation:

Mode	Description	Use Case
Cached (default)	Load pre-built polymers from SDF files	Reproducibility, specific sequences
Dynamic	Generate polymers from monomer SMILES	Flexibility, new monomers, rapid prototyping

Dynamic mode uses ATRP (Atom-Transfer Radical Polymerization) chemistry to:

1. Activate raw monomer SMILES via initiation reactions

2. Generate all possible polymer fragments

3. Build complete polymer chains with proper termination

4. Assign partial charges automatically

When to Use Dynamic Mode

Use Dynamic Mode when:

• You want to test new monomer chemistries quickly

• You don’t have pre-built polymer SDF files

• You want the system to handle fragment generation automatically

Use Cached Mode when:

• You need exact reproducibility of polymer structures

• You have validated, pre-built polymer SDFs

• You’re running production simulations with known good structures

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Quick Start

Here’s a minimal configuration for dynamic polymer generation:

name: "dynamic_polymer_test"

enzyme:
  name: "MyEnzyme"
  pdb_path: "structures/enzyme.pdb"

polymers:
  enabled: true
  generation_mode: "dynamic"      # Enable dynamic generation
  type_prefix: "SBMA-EGPMA"
  
  monomers:
    - label: "A"
      probability: 0.7
      name: "SBMA"
      smiles: "[H]C([H])=C(C(=O)OC([H])([H])C([H])([H])[N+](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])S(=O)(=O)[O-])C([H])([H])[H]"
    - label: "B"
      probability: 0.3
      name: "EGPMA"
      smiles: "[H]C([H])=C(C(=O)OC([H])([H])C([H])([H])Oc1c([H])c([H])c([H])c([H])c1[H])C([H])([H])[H]"
  
  length: 5
  count: 2
  charger: "nagl"

# ... rest of configuration (solvent, thermodynamics, etc.)

Then build and run:

polyzymd build -c config.yaml
polyzymd run-segment -c config.yaml -r 1

---

Configuration Reference

Generation Mode

polymers:
  generation_mode: "dynamic"    # or "cached" (default)

Value	Description
cached	Load polymers from pre-built SDF files (default)
dynamic	Generate polymers from monomer SMILES using ATRP chemistry

Monomer SMILES

In dynamic mode, each monomer requires a smiles field:

monomers:
  - label: "A"
    probability: 0.7
    name: "SBMA"
    smiles: "[H]C([H])=C(C(=O)..."    # Raw methacrylate SMILES
    residue_name: "SBM"               # Optional: 3-letter residue name

Field	Required	Description
label	Yes	Single character identifier (A, B, C…)
probability	Yes	Selection probability (must sum to 1.0)
name	Yes	Monomer name for identification
smiles	Yes (dynamic)	Raw monomer SMILES string
residue_name	No	3-letter residue name (auto-generated if not provided)

Important

SMILES Format: Provide the raw, unactivated monomer SMILES. For methacrylates, this means the structure with the C=C double bond intact. The system will handle activation (chlorination) automatically.

ATRP Reaction Configuration

By default, PolyzyMD uses bundled ATRP reaction templates. You can also specify custom reaction files:

polymers:
  generation_mode: "dynamic"
  
  reactions:
    initiation: "default"        # Use bundled template
    polymerization: "default"    # Use bundled template
    termination: "default"       # Use bundled template
  
  # Or specify custom reaction files:
  # reactions:
  #   initiation: "/path/to/my_initiation.rxn"
  #   polymerization: "/path/to/my_polymerization.rxn"
  #   termination: "/path/to/my_termination.rxn"

Charge Assignment

polymers:
  charger: "nagl"    # Charge method for polymer atoms

Method	Description	Speed
nagl	Graph neural network charges (recommended)	Fast
espaloma	Machine learning charges	Medium
am1bcc	Semi-empirical QM charges	Slow

Retry Configuration

Dynamic generation may occasionally produce structures with ring-piercing artifacts. The system automatically retries:

polymers:
  max_retries: 10    # Maximum attempts before failing (default: 10)

---

Complete Example Configuration

Here’s a complete configuration for running a simulation with dynamically generated polymers:

name: "LipA_dynamic_polymer_simulation"
description: "Lipase A with dynamically generated SBMA-EGPMA copolymers"

# Enzyme
enzyme:
  name: "LipA"
  pdb_path: "structures/enzyme.pdb"

# Substrate (optional)
substrate:
  name: "ResorufinButyrate"
  sdf_path: "structures/substrate.sdf"
  charge_method: "nagl"
  residue_name: "RBY"

# Dynamic Polymer Generation
polymers:
  enabled: true
  generation_mode: "dynamic"
  type_prefix: "SBMA-EGPMA"
  
  # ATRP reactions (use bundled defaults)
  reactions:
    initiation: "default"
    polymerization: "default"
    termination: "default"
  
  # Monomer definitions with SMILES
  monomers:
    - label: "A"
      probability: 0.7
      name: "SBMA"
      smiles: "[H]C([H])=C(C(=O)OC([H])([H])C([H])([H])[N+](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])S(=O)(=O)[O-])C([H])([H])[H]"
      residue_name: "SBM"
    - label: "B"
      probability: 0.3
      name: "EGPMA"
      smiles: "[H]C([H])=C(C(=O)OC([H])([H])C([H])([H])Oc1c([H])c([H])c([H])c([H])c1[H])C([H])([H])[H]"
      residue_name: "EGM"
  
  # Chain parameters
  length: 5
  count: 2
  
  # Charge assignment
  charger: "nagl"
  max_retries: 10
  
  # Caching
  cache_directory: ".polymer_cache"

# Solvent
solvent:
  primary:
    type: "water"
    model: "tip3p"
  co_solvents:
    - name: "dmso"
      volume_fraction: 0.30
      residue_name: "DMS"
  ions:
    neutralize: true
    nacl_concentration: 0.0
  box:
    padding: 1.2
    shape: "rhombic_dodecahedron"
    target_density: 1.05
    tolerance: 2.0

# Thermodynamics
thermodynamics:
  temperature: 300.0
  pressure: 1.0

# Simulation phases
simulation_phases:
  equilibration_stages:
    - name: "heating"
      duration: 0.2
      samples: 20
      ensemble: "NVT"
      temperature_start: 60.0
      temperature_end: 300.0
      temperature_increment: 1.0
      temperature_interval: 1200.0
      position_restraints:
        - group: "protein_heavy"
          force_constant: 4184.0
        - group: "polymer_heavy"
          force_constant: 4184.0
    - name: "free_equilibration"
      duration: 0.8
      samples: 80
      ensemble: "NPT"
      temperature: 300.0
  production:
    ensemble: "NPT"
    duration: 100.0
    samples: 2500
    time_step: 2.0
    thermostat: "LangevinMiddle"
    thermostat_timescale: 1.0
    barostat: "MC"
    barostat_frequency: 25
# Output
output:
  projects_directory: "."
  scratch_directory: null
  job_scripts_subdir: "job_scripts"
  slurm_logs_subdir: "slurm_logs"
  naming_template: "{enzyme}_{polymer_type}_dynamic_run{replicate}"
  save_checkpoint: true
  save_state_data: true
  trajectory_format: "dcd"

---

How Dynamic Generation Works

Step 1: Fragment Generation

When you run a simulation with generation_mode: "dynamic", the system:

1. Loads raw monomer SMILES from your configuration

2. Runs initiation reactions to activate the monomers (chlorination for ATRP)

3. Runs polymerization reactions to enumerate all possible fragments

4. Runs termination reactions on 1-site fragments to restore terminal alkenes

5. Creates a MonomerGroup with named fragments (e.g., SBMA_2-site, SBMA_1-site)

Step 2: Polymer Building

For each polymer chain:

1. Generate random sequence based on monomer probabilities (e.g., “AABBA”)

2. Set terminal orientations (head/tail use 1-site fragments)

3. Build 3D structure using Polymerist’s build_linear_polymer()

4. Validate no ring-piercing (retry if necessary)

5. Assign partial charges using the configured charger

Step 3: Caching

Generated fragments and polymers are cached for reuse:

.polymer_cache/
├── SBMA-EGPMA_monomer_group.json     # Fragment definitions
├── SBMA-EGPMA_AABBA_5-mer_charged.sdf  # Charged polymer structures
└── ...

To regenerate from scratch, delete the cache:

rm -rf .polymer_cache

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Supported Chemistries

ATRP (Atom-Transfer Radical Polymerization)

Currently, dynamic generation supports methacrylate-based monomers using ATRP chemistry:

• Sulfobetaine methacrylate (SBMA)

• Ethylene glycol phenyl ether methacrylate (EGPMA)

• Trimethylammonium ethyl methacrylate (TMAEMA)

• Sulfopropyl methacrylate (SPMA)

• Oligo(ethylene glycol) methacrylate (OEGMA)

Adding New Monomers

To use a new methacrylate monomer:

1. Obtain the SMILES string (with C=C double bond intact)

2. Add it to your configuration:

monomers:
  - label: "C"
    probability: 0.1
    name: "MyNewMonomer"
    smiles: "[H]C([H])=C(C(=O)O...)C([H])([H])[H]"

Note

For non-methacrylate monomers or different polymerization chemistries (e.g., ring-opening, condensation), you would need to provide custom reaction files. This is an advanced use case.

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Troubleshooting

“No 1-site terminal fragment found for monomer”

Cause: The cached MonomerGroup has old fragment names.

Solution: Delete the cache and regenerate:

rm -rf .polymer_cache

“Failed to build polymer after N attempts due to ring-piercing”

Cause: The polymer structure has atoms passing through rings.

Solutions:

1. Increase max_retries (default is 10)

2. Try shorter polymer chains

3. Check that monomer SMILES are correct

“Symbol ‘X’ not present in monomer group mapping”

Cause: Mismatch between sequence labels and MonomerGroup fragments.

Solution: Ensure all monomer labels (A, B, C…) in your config have corresponding fragments generated. Delete the cache and regenerate.

Slow fragment generation

Cause: First run generates all fragments, which can take time.

Solution: This is normal for the first run. Subsequent runs use the cached MonomerGroup and are much faster.

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Performance Tips

1. Start small: Test with short chains (length: 3-5) and few polymers (count: 1-2) first

2. Use NAGL charger: It’s much faster than AM1BCC for polymer charging

3. Reuse cache: Keep .polymer_cache between runs for the same monomer set

4. Parallelize later: Dynamic generation currently runs sequentially; HPC parallelization is planned

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See Also

• Polymer Setup Guide - General polymer configuration guide

• Configuration Reference - Complete configuration reference

• GROMACS Export and Simulation - Running with GROMACS