QDESCP (descriptor generation)

Overview

The QDESCP module implemented in AQME enables the automated calculation of molecular and atom-centered descriptors from either SMILES strings or three-dimensional structures. In the current implementation, descriptor generation is performed through MORFEUS, which acts as a unified interface to obtain electronic and steric descriptors.

Electronic descriptors are extracted from xTB calculations, preferentially using the PTB method when available and GFN2-xTB for descriptors not supported at the PTB level. In parallel, steric descriptors are computed directly from the GFN2-xTB-optimized geometries.

The overall workflow is summarized in this figure:

Workflow Description

1. Conformational search (if starting from SMILES)

When the starting point is a CSV file containing SMILES strings, conformational sampling is first performed using the CSEARCH workflow in AQME, typically employing RDKit (default) and optionally CREST.

The generated conformers are filtered using:

• An energy window (ΔE ≤ 5 kcal mol⁻¹)

• RMSD-based filtering

• Butina clustering

This process retains a structurally diverse subset of low-energy conformers (up to five conformers per molecule), which are stored as SDF files.

If three-dimensional structures are provided directly (e.g., XYZ or SDF files), the conformational search step is skipped, and the structures are used directly for descriptor generation.

2. Geometry optimization with GFN2-xTB

The resulting conformers are subsequently optimized at the GFN2-xTB level. This option can be skipped using xtb_opt=False (or --xtb_opt False in command line).

3. Descriptor generation

Through MORFEUS, both molecular and atom-centered descriptors are obtained from the optimized geometries. Descriptors are first computed for each conformer and subsequently Boltzmann-weighted to obtain a single descriptor set per molecule.

Applicability

The workflow is applicable to both organic and organometallic systems, provided that the underlying xTB calculations converge reliably.

Warning

As with other semiempirical approaches, the quality of the resulting descriptors depends on the robustness of the electronic structure calculations. Systems involving:

• Multireference character

• Excited states (i.e., S₁, S₂, T₁...)

• Aggregates or noncovalent complexes

should be interpreted with caution.

Output

The workflow produces CSV files containing Boltzmann-weighted descriptors corresponding to different descriptor subsets:

• interpret (default)

• denovo (reduced set)

• full (extended set including RDKit features)

Descriptor Table

Note

All citations for the descriptors and formulae can be found in our publication describing the descriptor‑generation workflow.

The final descriptor set combines 21 molecular descriptors and 18 atomic descriptors, including:

• xTB-based electronic descriptors (PTB method when available, if not GFN2-xTB)

• MORFEUS steric descriptors

Type	Full name	Descriptor	Definition / equation	Units	Method
Molecular	Highest occupied molecular orbital energy	HOMO	\(E_{\mathrm{HOMO}}\)	eV	PTB
Molecular	Lowest unoccupied molecular orbital energy	LUMO	\(E_{\mathrm{LUMO}}\)	eV	PTB
Molecular	HOMO–LUMO gap	HOMO–LUMO gap	\(E_{\text{gap}} = E_{\mathrm{LUMO}} - E_{\mathrm{HOMO}}\)	eV	PTB
Molecular	Ionization potential	IP	\(\mathrm{IP} = E(N-1) - E(N)\)	eV	GFN2
Molecular	Electron affinity	EA	\(\mathrm{EA} = E(N) - E(N+1)\)	eV	GFN2
Molecular	Molecular dipole moment magnitude	Dipole module	\(\text{-}\)	debye	PTB
Molecular	Solvent-accessible surface area	SASA	\(\mathrm{SASA} = \sum_i A_i\)	Ų	MORFEUS
Molecular	Dispersion surface area	Dispersion area	\(\text{-}\)	Ų	MORFEUS
Molecular	Dispersion volume	Dispersion volume	\(\text{-}\)	ų	MORFEUS
Molecular	Solvation free energy in water	G solv. in H₂O	\(\Delta G_{\text{solv}}\)	kcal/mol	GFN2
Molecular	Hydrogen-bond contribution to solvation	G of H-bonds H₂O	\(\Delta G_{\text{HB}}\)	kcal/mol	GFN2
Molecular	Fermi level	Fermi-level	\(E_F = \dfrac{E_{\mathrm{HOMO}} + E_{\mathrm{LUMO}}}{2}\)	eV	GFN2
Molecular	Molecular polarizability	Polarizability	\(\text{-}\)	a₀³	GFN2
Molecular	Chemical hardness	Hardness	\(\eta = \mathrm{IP} - \mathrm{EA}\)	eV	GFN2
Molecular	Chemical softness	Softness	\(S = \dfrac{1}{\eta}\)	eV⁻¹	GFN2
Molecular	Chemical potential	Chem. potential	\(\mu = -\dfrac{\mathrm{IP} + \mathrm{EA}}{2}\)	eV	GFN2
Molecular	Electrophilicity index	Electrophilicity	\(\omega = \dfrac{(\mathrm{IP}+\mathrm{EA})^2}{8(\mathrm{IP}-\mathrm{EA})} = \dfrac{\mu^2}{2\eta}\)	eV	GFN2
Molecular	Electrofugality	Electrofugality	\(\nu_{\text{electrofugality}} = \dfrac{(3\mathrm{IP}-\mathrm{EA})^2}{8(\mathrm{IP}-\mathrm{EA})} = \mathrm{IP} + \omega\)	eV	GFN2
Molecular	Nucleofugality	Nucleofugality	\(\nu_{\text{nucleofugality}} = \dfrac{(\mathrm{IP}-3\mathrm{EA})^2}{8(\mathrm{IP}-\mathrm{EA})} = -\mathrm{EA} + \omega\)	eV	GFN2
Molecular	Fractional occupation density	Total FOD	\(\text{-}\)	e	GFN2
Molecular	Singlet–triplet energy gap	S₀–T₁ gap	\(\Delta E_{S0\text{-}T1} = E_{T1} - E_{S0}\)	kcal/mol	GFN2
Atomic	Atomic hydrogen-bond contribution to solvation	H-bond H₂O	\(\Delta G_{\text{HB},i}\)	kcal/mol	GFN2
Atomic	Mulliken partial charge	Partial charge	\(q_i\)	e	PTB
Atomic	Atomic dipole moment magnitude	Dipole moment	\(\text{-}\)	debye	PTB
Atomic	Atom solvent accessible surface area	Atom SASA	\(A_i\)	Ų	MORFEUS
Atomic	Atomic dispersion descriptor	Atom dispersion	\(\text{-}\)	Ų	MORFEUS
Atomic	Percent buried volume	Buried volume	\(\text{-}\)	%	MORFEUS
Atomic	Pyramidalization parameter	Pyramidalization	\(P = \sin(\theta)·\cos(\alpha)\)	\(\text{-}\)	MORFEUS
Atomic	Pyramidalization angle	Pyramidaliz. volume	\(P = \sqrt{360^\circ - \sum_i \theta_i}\)	°	MORFEUS
Atomic	Fukui nucleophilic index	Fukui+	\(f^+ = q_N - q_{N+1}\)	\(\text{-}\)	GFN2
Atomic	Fukui electrophilic index	Fukui−	\(f^- = q_{N-1} - q_N\)	\(\text{-}\)	GFN2
Atomic	Radical Fukui index	Fukui_rad	\(f_{\mathrm{rad}} = \dfrac{q_{N-1} - q_{N+1}}{2}\)	\(\text{-}\)	GFN2
Atomic	Dual Fukui descriptor	Fukui dual	\(f^{(2)} = f^+ - f^-\)	\(\text{-}\)	GFN2
Atomic	Local electrophilicity	Electrophil.	\(l_\omega = -\dfrac{\mu}{\eta} f + \tfrac{1}{2}\dfrac{\mu}{\eta^2} f^{(2)}\)	\(\text{-}\)	GFN2
Atomic	Normalized electrophilicity	Normaliz. electrophil.	\(\omega_i = \omega\ · f_i^+\)	eV	GFN2
Atomic	Normalized nucleophilicity	Normaliz. nucleophil.	\(N_i = -\mathrm{IP}\ · f_i^-\)	eV	GFN2
Atomic	Atomic polarizability	Atom Polarizability	\(\text{-}\)	a₀³	GFN2
Atomic	Atomic FOD population	Atom FOD	\(\text{-}\)	e	GFN2
Atomic	Coordination number	Coord. numbers	\(\text{-}\)	\(\text{-}\)	GFN2