Glossary

Each abbreviation, method name, and unit used in the docs is defined here in one line, grouped by field. Options, output fields, and status values are on each command page and in JSON Output.

ML/MM & ONIOM

Term

Full Name

Description

ML/MM

Machine Learning / Molecular Mechanics

A multi-scale method that couples a machine-learning interatomic potential (for the reactive region) with a classical force field (for the surrounding environment). Analogous to QM/MM but with ML replacing QM.

ONIOM

Our own N-layered Integrated molecular Orbital and molecular Mechanics

A multi-layer energy decomposition scheme. mlmm-toolkit uses an ONIOM-like subtraction: E_total = E_REAL_low + E_MODEL_high - E_MODEL_low.

QM/MM

Quantum Mechanics / Molecular Mechanics

A multi-scale method coupling QM for the reactive region with MM for the environment. ML/MM replaces the QM layer with an MLIP backend.

Real system

—

The full set of atoms (all 3 layers). Evaluated at the MM (low) level in the ONIOM decomposition. Described by the parm7 topology; its MM energy is computed by the MM backend.

Model system

—

The ML region (Layer 1). Evaluated at both the MLIP (high) and MM (low) levels in the ONIOM decomposition.

Link Hydrogen

—

A hydrogen placed on each parm7 bond that crosses the ML/MM boundary. It lies along that bond, and its force is redistributed through a Jacobian. The cap hydrogens of extract --add-linkh are only for inspecting the pocket.

Link atom

—

See Link Hydrogen; in mlmm-toolkit the link atoms placed at severed ML/MM boundaries are hydrogens.

hessian_ff

—

A C++ native extension that evaluates Amber force field energies, forces, and analytical Hessians. Used as the MM engine in mlmm-toolkit.

3-layer system

—

mlmm-toolkit’s B-factor partitioning scheme: ML (B=0.0), Movable-MM (B=10.0), Frozen-MM (B=20.0).

B-factor encoding

—

Convention of storing layer membership in the PDB B-factor (temperature factor) column: 0.0 = ML, 10.0 = Movable-MM, 20.0 = Frozen-MM. Hessian-target MM is controlled by cutoffs/explicit indices. See The MM layers.

Amber & Force Field

Term

Full Name

Description

parm7

Amber Parameter/Topology File

A file containing atom types, partial charges, bonding connectivity, and force field parameters for an Amber system. Also called .prmtop.

rst7

Amber Restart File

A file containing atomic coordinates (and optionally velocities and box dimensions) for an Amber system. Also called .inpcrd.

AmberTools

—

A free suite of tools for molecular dynamics preparation, including tleap, antechamber, and parmchk2. Required by mlmm mm-parm.

tleap

—

An AmberTools program that builds Amber topology/coordinate files from PDB structures and force field libraries.

antechamber

—

An AmberTools program that assigns GAFF2 atom types and AM1-BCC partial charges to small molecules.

parmchk2

—

An AmberTools program that checks and supplies missing force field parameters for GAFF2 typing.

GAFF2

General Amber Force Field 2

A general-purpose force field for small organic molecules, used to parameterize non-standard residues (substrates, cofactors).

ff19SB

—

An Amber protein force field used for standard amino acid residues. The default in mlmm-toolkit.

ff14SB

—

An Amber protein force field (2014 version). Selectable with --ff-set ff14SB.

AM1-BCC

—

A charge model that combines AM1 (semi-empirical) Mulliken charges with bond charge corrections (BCC) to approximate HF/6-31G* RESP charges.

Reaction Path & Optimization

Term

Full Name

Description

MEP

Minimum Energy Path

The lowest-energy pathway connecting reactants to products through a transition state (on a potential energy surface).

TS

Transition State

A first-order saddle point on the potential energy surface — a stationary point with exactly one direction of negative curvature (one imaginary frequency) along the reaction coordinate.

n_imag

Number of imaginary modes

The number of vibrational modes below the imaginary-mode criterion (ν < −5.00 cm⁻¹ by default); a TS has n_imag = 1, and result.json records it as n_imaginary_modes (tsopt) or n_imaginary (freq).

IRC

Intrinsic Reaction Coordinate

A mass-weighted steepest-descent path from a TS toward reactants and products. Often used to validate TS connectivity.

GSM

Growing String Method

A string-based method that grows images from endpoints and optimizes them to approximate an MEP.

DMF

Direct Max Flux

A chain-of-states method for optimizing an MEP by maximizing flux along the pathway. In mlmm-toolkit it is selected with --mep-mode dmf.

HEI

Highest-Energy Image

The image along an MEP with maximum energy; often used as a TS guess.

Image

—

A single geometry (one “node”) along a chain-of-states path.

Segment

—

An MEP between two adjacent endpoints (e.g., R → I1, I1 → I2, …).

Kink

—

A segment where only the conformation changes: the two structures that path-search optimizes on either side of the HEI (End1 and End2; path-search → How it works, step 2) differ by no covalent bond change. path-search fills it with a few linearly interpolated nodes (search.kink_max_nodes, default 3) and optimizes each one instead of running a new GSM or DMF path.

Optimization Algorithms

Term

Full Name

Description

L-BFGS

Limited-memory BFGS

A quasi-Newton optimization algorithm that approximates the Hessian using a limited history of gradients. Used in opt --opt-mode grad.

RFO

Rational Function Optimization

A trust-region optimization method that uses explicit Hessian information. Used in --opt-mode hess.

RS-I-RFO

Restricted-Step Image-RFO

A variant of RFO for saddle point (TS) optimization that follows one negative eigenvalue.

Dimer

Dimer Method

A TS optimization method that follows a low-curvature direction. mlmm-toolkit’s Hessian-guided variant uses initial and periodic active-subspace Hessians, which is more robust than a random initial orientation for systems with many active degrees of freedom. Used in --opt-mode grad for TSOPT.

PHVA

Partial Hessian Vibrational Analysis

Computing vibrational frequencies using only the Hessian block for active (non-frozen) atoms. Default in freq.

Machine Learning & Calculators

Term

Full Name

Description

MLIP

Machine Learning Interatomic Potential

A model (often neural-network-based) that predicts energies and forces from atomic structures, trained on quantum-mechanical data.

UMA

Universal Models for Atoms

Meta’s family of pretrained MLIPs. The default ML backend in mlmm-toolkit (--backend uma).

ORB

ORB Models

A family of pretrained MLIPs from Orbital Materials. Supported as an alternative ML backend (--backend orb). Install with pip install "mlmm-toolkit[orb]".

MACE

MACE (Message-passing Atomic Cluster Expansion)

A message-passing equivariant neural network MLIP. Supported as an alternative ML backend (--backend mace). Install in a separate conda env: pip uninstall fairchem-core (UMA pin clashes on e3nn), then pip install mace-torch.

AIMNet2

Atoms In Molecules Network 2

A neural network potential for organic molecules. Supported as an alternative ML backend (--backend aimnet2). Install with pip install "mlmm-toolkit[aimnet]".

Analytical Hessian

—

Computing second derivatives through the backend’s differentiable/native Hessian path. Runtime and memory are backend- and system-dependent. Supported by UMA, ORB, MACE, and AIMNet2.

Finite Difference

—

Approximating derivatives from displaced-force evaluations. Runtime and memory are backend- and system-dependent. Available for every MLIP backend.

Quantum Chemistry

Term

Full Name

Description

QM

Quantum Mechanics

First-principles electronic structure calculations (DFT, HF, post-HF, etc.).

DFT

Density Functional Theory

A quantum-mechanical method that models electronic structure via electron density functionals.

Hessian

—

The matrix of second derivatives of energy with respect to atomic coordinates; used for vibrational analysis and TS optimization.

SP

Single Point

A calculation at a fixed geometry (no optimization); often used for higher-level energy refinement.

Spin Multiplicity

—

2S+1, where S is total spin. Singlet = 1, doublet = 2, triplet = 3, etc.

Structural Biology & Pocket Extraction

Term

Full Name

Description

PDB

Protein Data Bank

A file format and database for macromolecular 3D structures.

XYZ

—

A simple text format listing atomic symbols and Cartesian coordinates. The calculation commands accept XYZ together with --ref-pdb.

GJF

Gaussian Job File

An input format for Gaussian; oniom-export writes it in g16 mode, and oniom-import and bond-summary read it.

Pocket

Active-site Pocket

A truncated structure around the substrate(s), extracted by the extract subcommand. In the ML/MM workflow, this defines the ML region and surrounding MM environment.

Extractor-only Link Hydrogen

—

A cap hydrogen that extract --add-linkh adds so that you can inspect the pocket. ML/MM calculations do not use it: the link pairs come from the parm7 bonds at the ML/MM boundary.

Backbone

—

The main chain of a protein (N–Cα–C–O atoms). Can be excluded during pocket extraction with --exclude-backbone.

B-factor

Temperature Factor

The PDB temperature factor column. In mlmm-toolkit, used to encode 3-layer membership (0.0, 10.0, 20.0).

Thermochemistry

Term

Full Name

Description

ZPE

Zero-Point Energy

The vibrational energy at 0 K; a quantum correction to the electronic energy.

Gibbs Energy

Gibbs Free Energy (G)

G = H − TS; includes thermal and entropic contributions.

Enthalpy

(H)

H = E + PV; total heat content at constant pressure.

Entropy

(S)

A measure of disorder; contributes −TS to Gibbs energy.

QRRHO

Quasi-Rigid-Rotor Harmonic Oscillator

A thermochemical approximation incorporating Grimme’s correction for low-frequency vibrations. Automatically applied in freq.

Units & Constants

Term

Description

Hartree

Atomic unit of energy; 1 Hartree ≈ 627.5 kcal/mol ≈ 27.21 eV.

kcal/mol

Kilocalories per mole; a common unit for reaction energetics.

kJ/mol

Kilojoules per mole; 1 kcal/mol ≈ 4.184 kJ/mol.

eV

Electron volt; 1 eV ≈ 23.06 kcal/mol.

Bohr

Atomic unit of length; 1 Bohr ≈ 0.529 Å.

Angstrom (Å)

10⁻¹⁰ m; standard unit for interatomic distances.

cm⁻¹

Reciprocal centimeters (wavenumber); the standard unit for vibrational frequencies. Imaginary frequencies appear as negative values.

Imaginary Frequency

A vibrational frequency corresponding to a negative eigenvalue of the Hessian. A TS has exactly one (first-order saddle point). Reported as a negative cm⁻¹ value.

Imaginary-mode criterion and QRRHO rotor cutoff

Imaginary-mode classification and the QRRHO rotor cutoff serve different purposes:

Threshold

Role

Source

ν < −5.00 cm⁻¹

Default imaginary-mode criterion.

Configurable: freq.zero_cutoff_cm.

100 cm⁻¹

QRRHO rotor cutoff (Grimme). Positive low-frequency vibrations are damped between harmonic-oscillator and free-rotor entropy in freq thermochemistry; it changes only entropy / Gibbs free energy.

Fixed (not configurable in mlmm-toolkit).

CLI Conventions

Boolean options, residue selectors, and atom selectors are described in Common options and selectors.

Notes

  • Imaginary modes and negative signs: n_imag counts only the modes below the imaginary-mode criterion. Every frequency is still reported with its sign, and the count of all negative values (n_negative_modes in result.json) is a separate diagnostic that does not change convergence.

See Also