Glossary

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 — a stationary point with exactly one direction of negative curvature (one imaginary frequency) 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.

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).

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	Atoms-in-Molecules Neural Network Potential, 2nd generation	Charge-aware neural-network potential (Anstine et al., Chem. Sci. 2025); 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.
ASE	Atomic Simulation Environment	Python framework providing the Calculator API used by all MLIP backends in pdb2reaction (Larsen et al., J. Phys. Condens. Matter 2017).
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	—	Approximation of the Hessian via finite nuclear displacements; slower but more memory-efficient. Selected with --hessian-calc-mode FiniteDifference (default).

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).
CPCM-X	Extended Conductor-like Polarizable Continuum Solvation Model	An implicit-solvent model available via xTB (--solvent-model cpcmx); “X” stands for “eXtended”, obtained by coupling CPCM with COSMO-RS-style σ-profiles and an SMD-style non-electrostatic term to give realistic solvation free energies for arbitrary solvents (Stahn, Ehlert, Grimme, J. Phys. Chem. A 2023).
cyipopt	—	Python bindings for the IPOPT interior-point optimizer. Required by the DMF (--mep-mode dmf) path refinement pipeline.
IPOPT	Interior Point OPTimizer	Open-source nonlinear constrained optimizer (Wächter & Biegler 2006) used by the DMF path-refinement solver via cyipopt bindings.
SCF	Self-Consistent Field	Iterative procedure that converges the electronic wavefunction in DFT/HF; controlled in pdb2reaction dft by --max-cycle and --conv-tol.

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 cap 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 hydrogen atoms (cap hydrogens).
Cap 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.

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.
RMSD	Root-Mean-Square Deviation; used as the segment stitch / bridge similarity metric in path-search (stitch_rmsd_thresh, bridge_rmsd_thresh).
MAE	Mean Absolute Error; used in benchmark / regression reports.
CI	Confidence Interval (statistical context). Distinct from quantum-chemistry “configuration interaction”; pdb2reaction uses CI only in benchmark statistics.
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. The detection threshold is hessian_dimer.neg_freq_thresh_cm (default 5 cm⁻¹).

Frequency thresholds: 5 cm⁻¹ imaginary detection vs 100 cm⁻¹ QRRHO rotor cutoff

Two unrelated cm⁻¹ thresholds appear in pdb2reaction. They act on different mode populations and serve different purposes:

Threshold	Role	Source
5 cm⁻¹	Imaginary-mode detection cutoff. Negative eigenvalues with magnitude below this are not counted as imaginary (treated as rigid-body / numerical noise).	pdb2reaction/core/defaults.py as hessian_dimer.neg_freq_thresh_cm = 5.0; tunable via YAML.
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.	thermoanalysis/config.py as ROTOR_CUT_DEFAULT = 100.0.

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.

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