Glossary

AMBER: Assisted Model Building with Energy Refinement. A family of force fields and a suite of molecular dynamics programs widely used for biomolecular simulations. In this tutorial, pmemd.cuda and sander are the primary executables.
Antechamber: An AMBER tool that automates the assignment of atom types and partial charges for small organic molecules. Used in Ligand Parametrisation with Antechamber to generate GAFF2 parameters for the oxime substrate.
CM5 charges: Class IV charge model, variant 5. Atomic point charges derived from Hirshfeld population analysis and corrected for long-range electrostatics. Computed here using Gaussian as the external QM package.
Collective Variable (CV): A reaction coordinate that describes the progress of a chemical or conformational transformation. In QM/MM Steered Molecular Dynamics (SMD) the CV is a linear combination of distances (LCOD) encoding the hydride transfer from flavin N5 to substrate N1.
Electronic embedding: A QM/MM coupling scheme in which the MM point charges are included in the QM Hamiltonian. This polarises the QM wavefunction by the electrostatic environment of the protein. Activated by qmmm_int = 1 in AMBER.
FMNH⁻ / FMN: Flavin mononucleotide. The reduced form (FMNH⁻) carries the hydride at N5 of the isoalloxazine ring and acts as the hydride donor in Old Yellow Enzyme reactions. Abbreviated as FMH in the AMBER topology used in this tutorial.
Force field: A mathematical model describing the potential energy of a molecular system as a sum of bonded (bonds, angles, torsions) and non-bonded (van der Waals, electrostatics) terms. This tutorial uses ff19SB for the protein and GAFF2 for the ligands.
Free energy profile: The change in free energy along a reaction coordinate, computed here from QM/MM SMD trajectories using the fluctuation-dissipation (FD) estimator. Equivalent to a potential of mean force (PMF) when sampled sufficiently.
GAFF2: General AMBER Force Field version 2. An extension of the standard AMBER force field designed for small organic molecules. Parameters are stored in $AMBERHOME/dat/leap/parm/gaff2.dat.
Hirshfeld charges: Atomic partial charges derived by partitioning the electron density according to the weight of the promolecular density of each atom. The basis for CM5 charges. Requested in Gaussian via pop=hirshfeld.
HOMO-LUMO gap: The energy difference between the Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO). A gap of zero indicates a problematic electronic state. Monitoring this during QM/MM MD is recommended to detect SCF convergence failures.
Link atom: A hydrogen atom inserted at the QM/MM boundary to cap a severed covalent bond. It satisfies the valency of the outermost QM atom and is invisible to the MM region. Handled automatically by AMBER sander.
MM region: The part of the system described by classical molecular mechanics force field parameters. In this tutorial all protein atoms outside the QM mask, water molecules, and counter-ions form the MM region.
NBO: Natural Bond Orbital. A mathematical transformation of the Kohn-Sham or Hartree-Fock orbitals into an orthonormal set that closely resembles the Lewis dot structure picture of bonding. Used in Natural Bond Orbital (NBO) Analysis to track bond order changes along the reaction coordinate.
NPT ensemble: Molecular dynamics at constant particle number (N), pressure (P) and temperature (T). Used during equilibration to allow the system volume to relax to the correct density.
NVT ensemble: Molecular dynamics at constant particle number (N), volume (V) and temperature (T). Used during thermalisation in System Equilibration and Minimisation.
Old Yellow Enzyme (OYE): A family of flavin-dependent oxidoreductases. XenA (Xenobiotic reductase A) belongs to the OYE-3 subfamily and is the enzyme studied in this tutorial.
prmtop / parm7: The AMBER topology file containing force field parameters, atom types, charges, and connectivity for the entire system. Generated by tLEaP and read by all AMBER MD programs.
QM region: The subset of atoms treated with a quantum mechanical method (B3LYP/6-31G* here). Selected via the qmmask keyword in the AMBER .in file. In this tutorial the QM4 region comprises the substrate, lumiflavin, and four active-site residues.
QM/MM: Combined Quantum Mechanics / Molecular Mechanics. A multi-scale method in which a chemically important region (the active site) is treated with QM, while the surrounding protein and solvent are described by classical MM. The two regions are coupled electrostatically via electronic embedding.
rst7: The AMBER coordinate/restart file containing atomic positions and velocities at a given point in a simulation. Passed to subsequent steps via the -c flag.
SHAKE: A constraint algorithm that removes high-frequency bond vibrations involving hydrogen atoms, allowing a 2 fs time step. Activated by ntc=2, ntf=2 in AMBER.
SMD: Steered Molecular Dynamics. An enhanced sampling method that applies a time-dependent harmonic restraint (the “steering force”) to a collective variable, driving the system along a predefined reaction coordinate. The work done by the steering force is used to estimate the free energy change.
SQM: Semi-empirical Quantum Mechanics. A computationally inexpensive QM method (PM6-DH+ in this tutorial) used for a preliminary QM/MM minimisation step before the more expensive DFT-based QM/MM minimisation.
TeraChem: A GPU-accelerated quantum chemistry package developed by PetaChem. Used as the external QM engine for B3LYP/6-31G* calculations in this tutorial via AMBER’s file-based interface (qm_theory = 'EXTERN').
tLEaP: The AMBER program for building molecular topology and coordinate files. Used in System Setup with tLEaP to combine the protein, cofactor, substrate, water and ions into a single solvated system.
VDD charges: Voronoi Deformation Density charges. Atomic partial charges obtained by integrating the deformation density (the difference between the molecular and promolecular electron density) over Voronoi cells. Computed in TeraChem via poptype vdd.
XenA: Xenobiotic reductase A. An ene-reductase from Pseudomonas putida belonging to the Old Yellow Enzyme family. XenA reduces the carbon-carbon double bond of electron-poor alkenes using FMNH⁻ as the hydride donor. Crystal structure available as PDB entry 8AU8.