Grouping Strategies

This page provides detailed documentation for each molecular structure grouping strategy available in chemsmart.

RMSD-based Strategies

rmsd (Basic RMSD)

Simple Kabsch RMSD alignment without atom reordering.

chemsmart run grouper -f conformers.xyz rmsd

Default threshold: 0.5 Å

This is the fastest RMSD method but assumes atoms are already in the same order. Best for structures from the same source with consistent atom ordering.

hrmsd (Hungarian RMSD)

RMSD with optimal atom mapping using the Hungarian algorithm (J. Chem. Inf. Model. 2014, 54, 518).

chemsmart run grouper -f conformers.xyz hrmsd

Default threshold: 0.5 Å

Finds the optimal one-to-one mapping between atoms of the same element type that minimizes RMSD. Useful when atom ordering may differ.

spyrmsd

RMSD calculation using the spyrmsd library with symmetry handling (J. Cheminformatics 2020, 12, 49).

chemsmart run grouper -f conformers.xyz spyrmsd

Default threshold: 0.5 Å

Handles molecular symmetry and equivalent atom permutations using graph isomorphism.

irmsd (Invariant RMSD)

Invariant RMSD that considers molecular symmetry and equivalent atom permutations (J. Chem. Inf. Model. 2025, 65, 4501).

chemsmart run grouper -f conformers.xyz irmsd
chemsmart run grouper -f conformers.xyz -T 0.3 irmsd --inversion on

Default threshold: 0.125 Å

Strategy-specific Options

Option	Type	Description
--inversion	choice	Coordinate inversion checking: auto (default), on, off

Note: Requires the external irmsd package installed in a separate conda environment with numpy>=2.0. See installation instructions in the README.

pymolrmsd

PyMOL-based RMSD alignment using the align command (Schrödinger, L. The PyMOL Molecular Graphics Development Component, Version 1.8; 2015).

chemsmart run grouper -f conformers.xyz pymolrmsd

Default threshold: 0.5 Å

Uses PyMOL’s powerful alignment algorithm. Note that PyMOL only supports single-threaded operation (-np 1).

Fingerprint-based Strategies

tfd (Torsion Fingerprint Deviation)

Compare conformers based on their torsion angle fingerprints (J. Chem. Inf. Model. 2012, 52, 1499).

chemsmart run grouper -f conformers.xyz tfd
chemsmart run grouper -f conformers.xyz -T 0.2 tfd --no-use-weights
chemsmart run grouper -f conformers.xyz tfd --max-dev spec

Default threshold: 0.1

Particularly effective for flexible molecules where conformational differences are primarily due to bond rotations.

Strategy-specific Options

Option	Type	Description
--use-weights/--no-use-weights	bool	Use torsion weights in TFD calculation (default: True)
--max-dev	choice	Normalization method: equal (default) or spec

tanimoto

Group structures using Tanimoto similarity with molecular fingerprints.

chemsmart run grouper -f conformers.xyz tanimoto
chemsmart run grouper -f conformers.xyz -T 0.85 tanimoto --fingerprint-type morgan

Default threshold: 0.9

Strategy-specific Options

Option	Type	Description
-ft, --fingerprint-type	choice	Fingerprint type (default: rdkit)

Available fingerprint types:

• rdkit / rdk: RDKit topological fingerprints

• morgan: Morgan circular fingerprints (ECFP-like)

• maccs: MACCS keys

• atompair: Atom pair fingerprints

• torsion: Topological torsion fingerprints

• usr: Ultrafast Shape Recognition (3D shape-based)

• usrcat: USR with Credo Atom Types (3D shape-based)

Energy-based Strategies

energy

Group molecules based on their energy differences.

chemsmart run grouper -f conformers.xyz energy
chemsmart run grouper -f conformers.xyz -T 0.5 energy

Default threshold: 1.0 kcal/mol

Note: All molecules must have energy information. For xyz files, energy is read from the comment line. For log files, Gibbs free energy is calculated as SCF energy + thermal correction.

Other Strategies

formula

Group molecules by their molecular formula.

chemsmart run grouper -f molecules.xyz formula

This is a quick way to separate different compounds in a mixed set.

connectivity

Group molecules by their molecular connectivity/topology.

chemsmart run grouper -f molecules.xyz connectivity

Groups molecules that have the same bond connectivity graph, regardless of 3D geometry.

isomorphism

Group molecules based on graph isomorphism using RDKit.

chemsmart run grouper -f molecules.xyz isomorphism

Similar to connectivity but uses RDKit’s isomorphism checking.

Complete Linkage

All threshold-based grouping strategies use complete linkage clustering, which ensures that all members within a group are within the threshold distance of each other. This prevents the “chaining effect” where dissimilar structures could end up in the same group through intermediate structures.