Glossary

This page provides definitions for abbreviations and technical terms used throughout the pdb2reaction documentation.

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Reaction Path & Optimization

Term	Full Name	Description
MEP	Minimum Energy Path	The lowest-energy pathway on a potential energy surface (PES) connecting reactants to products through a transition state.
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	Classically defined as the mass-weighted steepest-descent path from a TS toward reactants and products, used to validate TS connectivity. In pdb2reaction the EulerPC integrator runs in unweighted Cartesian coordinates (irc.md: --step-size is in Bohr of unweighted Cartesian); geom.coord_type is forced to cart.
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 pdb2reaction 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, …).
Reactive segment	—	A segment in which covalent bond changes are detected between the endpoints. Only reactive segments proceed to TS optimization.
Bridge segment	—	A segment connecting two non-adjacent intermediates that still contains unresolved bond changes; path-search recursively subdivides bridge segments until all reactive regions are isolated.
Kink	—	A region along an MEP where no covalent bond change is detected but a geometric distortion persists. path-search inserts linearly interpolated nodes and optimizes them individually rather than running a full string calculation.
PES	Potential Energy Surface	A hypersurface of energy as a function of atomic coordinates. The MEP is the lowest-energy pathway on the PES.

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Optimization Algorithms

Term	Full Name	Description
BFGS	Broyden-Fletcher-Goldfarb-Shanno	A quasi-Newton Hessian update scheme (hessian_update: bfgs).
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 --opt-mode hess.
RS-I-RFO	Restricted-Step Image-RFO	A variant of RFO for saddle point (TS) optimization that follows one negative eigenvalue. Default for tsopt --opt-mode hess.
Dimer	Dimer Method	A TS optimization method that estimates the lowest curvature mode without computing the full Hessian. Used in tsopt --opt-mode grad. pdb2reaction uses a Hessian-Guided Dimer variant that periodically evaluates an exact active-subspace Hessian to update the dimer direction.
Bofill	Bofill Update	A Hessian update scheme that blends SR1 (symmetric rank-one) and PSB (Powell-symmetric-Broyden) updates, well suited to saddle-point searches. Selected via hessian_update: bofill and used by RS-I-RFO and the Dimer flatten loop.
SR1	Symmetric Rank-One	A rank-one Hessian update scheme; one of the two components blended by Bofill.
PSB	Powell-Symmetric-Broyden	A symmetric Hessian update scheme; the second component blended by Bofill.
EulerPC	Euler Predictor-Corrector	An integration scheme for IRC calculations: a predictor step along the gradient direction followed by a corrector step that refines the path.
PHVA	Partial Hessian Vibrational Analysis	Vibrational analysis performed only on the active (non-frozen) degrees of freedom. Automatically applied when freeze_atoms is set.
Active DOF	Active Degrees of Freedom	The 3N Cartesian coordinates of atoms not listed in freeze_atoms. PHVA, partial-Hessian TS optimization, and the analytical Hessian path operate only on this active subspace; frozen atoms contribute neither rows nor columns to the reduced Hessian.
DLC	Delocalized Internal Coordinates	A redundant internal coordinate system constructed from interatomic distances, angles, and dihedrals. Available via coord_type: dlc (default is cart = Cartesian).

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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 used as the default calculator backend in pdb2reaction.
ORB	ORB Models	Orbital Materials’ MLIP backend. Selected with -b orb.
MACE	MACE	Equivariant message-passing MLIP. Selected with -b mace.
AIMNet2	AIMNet2	Atoms-In-Molecules Network v2. Selected with -b aimnet2.
xTB	Extended Tight Binding	A semi-empirical quantum chemistry method. In pdb2reaction, used for implicit solvation correction via --solvent.
fairchem	—	Meta’s open-source foundation-model toolkit that ships the UMA family of checkpoints. pdb2reaction depends on fairchem-core to load UMA predictors.
task_name	—	UMA task tag recorded in each inference batch (YAML: calc.task_name, default omol). Selects the UMA task/preset that a checkpoint was trained for.
Analytical Hessian	—	Exact evaluation of the Hessian matrix via automatic differentiation; faster than finite differences but requires more VRAM. Selected with --hessian-calc-mode Analytical.
Finite Difference	—	Approximating the Hessian by finite nuclear displacements; slower but more memory-efficient. Selected with --hessian-calc-mode FiniteDifference (default).

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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.
DFT//MLIP	—	Composite-method notation: DFT single-point energies evaluated at MLIP-optimized geometries. Combines MLIP geometry/dynamics with DFT energy refinement. The // separator follows the standard quantum-chemistry convention “energy-level // geometry-level”.
Hessian	—	The matrix of second derivatives of energy with respect to atomic coordinates. Eigenvalues yield vibrational frequencies; eigenvectors yield vibrational modes (displacement vectors). 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. Specified with -m/--multiplicity (default: 1).
ALPB	Analytical Linearized Poisson-Boltzmann	An implicit-solvent model available via xTB (--solvent-model alpb, default).
CPCMX	Conductor-like PCM (exchange-correlation extension)	An implicit-solvent model available via xTB (--solvent-model cpcmx).
cyipopt	—	Python bindings for the IPOPT interior-point optimizer. Required by the DMF (--mep-mode dmf) path refinement pipeline.

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Structural Biology & Active Site Model 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; pdb2reaction reads charge/multiplicity and coordinates from these files.
Active Site Model	Active Site Model (Binding Pocket)	The extraction region around the substrate(s), defined by -c/--center and -r/--radius. pdb2reaction uses “active site model” and “cluster model” interchangeably when describing the downstream calculation input; strictly, “active site model” refers to the geometric selection and “cluster model” to the same selection after it has been capped with link hydrogens and prepared for QM/MLIP calculation.
Cluster Model	—	The QM/MLIP computational subsystem obtained by taking the extracted active site model and capping severed covalent bonds with link hydrogens. In practice, “active site model” (pre-cap geometric selection) and “cluster model” (capped, calculation-ready) name two stages of the same object.
Link Hydrogen	—	A hydrogen atom added to cap severed bonds when extracting an active site model from a larger structure.
Backbone	—	The main chain of a protein (N–Cα–C–O atoms). Can be excluded during active site model extraction with --exclude-backbone.

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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.

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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. See Imaginary-mode thresholds: 5 cm⁻¹ vs 100 cm⁻¹ for the two separate thresholds used by pdb2reaction.

Imaginary-mode thresholds: 5 cm⁻¹ vs 100 cm⁻¹

pdb2reaction uses two distinct cm⁻¹ thresholds around imaginary modes, which are easy to confuse:

Threshold	Role	Where defined	Nature
5 cm⁻¹	Internal detection cutoff — frequencies with magnitude below this are not counted as imaginary at all (treated as rigid-body / numerical noise).	pdb2reaction/defaults.py as hessian_dimer.neg_freq_thresh_cm = 5.0	Hard-coded default; tunable via hessian_dimer.neg_freq_thresh_cm in YAML.
100 cm⁻¹	TS-quality gate — user-facing heuristic: a physically meaningful TS imaginary mode should have |ν| ≥ 100 cm⁻¹ along the reaction coordinate. Below this, the “imaginary” mode is likely a soft wag or rotational artefact, not a true reaction coordinate.	recipes-common-errors.md and troubleshooting.md TS-quality checks	Not a code threshold; a reader heuristic.

These thresholds answer different questions: 5 cm⁻¹ decides “is this counted as imaginary?”; 100 cm⁻¹ decides “does this imaginary mode look like a real TS?”. Don’t conflate them — a mode at, say, 35 cm⁻¹ is counted as imaginary internally (passes the 5 cm⁻¹ filter) but fails the TS-quality gate (below 100 cm⁻¹).

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CLI Conventions

Term	Description
Boolean option	CLI flags that accept toggle form (--flag / --no-flag) or value form (True/False, yes/no, 1/0). 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.

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See Also

• Getting Started — installation and a first run

• Installation — setup and dependencies

• all — how active site model extraction, MEP search, and post-processing fit together

• Common Error Recipes — symptom-first failure routing

• Troubleshooting — common errors and fixes

• YAML Reference — configuration file format

• MLIP Calculator — machine learning potential details