Glossary

This page provides definitions for abbreviations and technical terms used throughout the mlmm-toolkit documentation.

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; MM energy computed by hessian_ff.

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 atom added to cap severed bonds at the ML/MM boundary during pocket extraction. Forces are redistributed via a Jacobian.

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 (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. Hessian-target MM is controlled by cutoffs/explicit indices.

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, typically the highest-energy point along the reaction coordinate.

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.

NEB

Nudged Elastic Band

A chain-of-states method that uses spring forces to maintain image spacing along a reaction path.

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,…).

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-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 estimates the lowest curvature mode without computing the full Hessian. 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 Machine-learning potential for Atoms

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

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). Requires a separate environment due to e3nn conflicts (see README).

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[aimnet2]".

xTB

Extended Tight-Binding

A semi-empirical quantum chemistry method. Used for point-charge embedding correction when --embedcharge is enabled.

Analytical Hessian

–

Computing the exact second derivatives of energy; faster but requires more VRAM. Currently available for the UMA backend only.

Finite Difference

–

Approximating derivatives by small displacements; slower but more memory-efficient. Used by ORB, MACE, and AIMNet2 backends.

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.

GJF

Gaussian Job File

An input format for Gaussian; mlmm-toolkit reads charge/multiplicity and coordinates from these files.

Pocket

Active-site Pocket

A truncated structure around the substrate(s) used to reduce system size for MEP/TS search. Also called “cluster model”.

Cluster Model

–

Synonym for pocket; a computationally tractable subset of the full enzyme-substrate complex.

Link Hydrogen

–

A hydrogen atom added to cap severed bonds when extracting a pocket from a larger structure.

Backbone

–

The main chain of a protein (N-C_alpha-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

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.

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 Angstrom.

Angstrom

10^-10 m; standard unit for atomic distances.

CLI Conventions

Term

Description

Boolean option

CLI flags that take True or False (capitalized). Example: --tsopt.

Residue selector

A specification like 'SAM,GPP' (names) or 'A:123,B:456' (chain:ID).

Atom selector

A specification like 'TYR,285,CA' identifying a specific atom by residue name, number, and atom name.

B-factor layer encoding

The convention of using the PDB B-factor column to encode 3-layer assignments (0.0, 10.0, 20.0). Hessian-target MM atoms are controlled separately.

See Also