chem-conformer-search

Molecular Conformer Search & Ranking

Goal

Generate a diverse ensemble of low-energy conformers for a given molecule. The workflow combines:

1. Stochastic sampling using RDKit's ETKDG algorithm (Experimental Torsion Distance Geometry).
2. High-accuracy relaxation using Machine Learning Interatomic Potentials (MLIPs) to get near-DFT quality geometries and energies.
3. Deduplication and Boltzmann weighting to identify the most relevant conformers at finite temperature.

[!IMPORTANT] This skill is optimized for organic molecules and uses MACE-OFF23 models by default. For inorganic clusters, switch to MACE-OMAT or MatGL models.

Recommended Models

• MACE-OFF23: MACE-OFF23-small (default), MACE-OFF23-medium — trained on organic molecules (Env: mace-agent)
• MACE-MH: MACE-MH-1 with head omol — multi-head model with molecular head (Env: mace-agent)
• UMA: uma-s-1p1 with head omol — general molecular model (Env: fairchem-agent)

1. Prerequisites

• Conda Environment: mace-agent (recommended as it includes both mace and rdkit).
• Input: SMILES string or a structure file (.xyz, .sdf, .mol2, .pdb).

2. Methodology

1. Generation: Generate N initial conformers using RDKit's EmbedMultipleConfs with ETKDGv3.
2. Relaxation: Optimize the geometry of each conformer using the selected MLIP (fmax = 0.01 eV/Å).
3. Deduplication/Clustering: Filter redundant conformers by simple RMSD thresholding (default), Hierarchical clustering, or K-Means clustering. Only the lowest-energy conformer in each cluster is kept.
4. Ranking: Sort unique conformers by energy.
5. Boltzmann Weighting: Calculate population probability $P_i$ at temperature $T$: $$P_i = \frac{e^{-(E_i - E_{min}) / k_B T}}{\sum_j e^{-(E_j - E_{min}) / k_B T}}$$

3. Usage

Basic Usage (SMILES)

Generate 30 conformers for a molecule (e.g., aspirin) and relax with MACE-OFF23:

# Env: mace-agent
python .agents/skills/chem-conformer-search/scripts/conformer_search.py \
    --smiles "CC(=O)Oc1ccccc1C(=O)O" \
    --num_conformers 30 \
    --output_dir research/aspirin_conformers