# Chemistry with Propab

Compound data, docking, quantum chemistry, molecular dynamics and materials screens, run at the scale the question needs and checked against what is known.

## Real runs

- **Cheminformatics** — [replay](https://propabai.com/replay/share_a_cIvoLdi-04i_7nZVYPu0PdFt1YfMYt): “For EGFR, pull measured inhibitors from ChEMBL, filter them by drug-likeness, cluster them by scaffold, and pick 20 diverse candidates for testing with a rationale. Deliver a chemical-space plot, the candidate table and a short report.” Made: Chemical space, Candidate table, Report.

## Workflows ready today

### Analytical chemistry

- **Identify an unknown from its EI mass spectrum** — Library search of a 70 eV EI spectrum with a calibrated accept/refuse threshold, so 'not in the library' is a possible answer.
- **Process an NMR FID into a quantitative spectrum** — Phased, referenced 1D spectrum with an integral table; qNMR purity against an internal standard.
- **Quantify an analyte by chromatography** — Integrated peaks, internal-standard calibration, concentration and expanded uncertainty from raw traces.
- **Resolve two co-eluting peaks** — Deconvolved areas of overlapping peaks and whether the separation is adequate.
- **Molecular formula from accurate mass** — Candidate formulas ranked by mass error and isotope-pattern fit.
- **Untargeted LC-MS feature table** — Detected, aligned and annotated features across an LC-MS run set, with spectral-library matches.
- **Multivariate calibration of spectra** — PLS calibration or PCA of a spectral set, with cross-validated error and outliers flagged.
- **Validate an analytical method** — Linearity, accuracy, precision, LOD/LOQ and a GUM uncertainty budget to ICH Q2 / Eurachem.

### Cheminformatics

- **Build a modelling table from ChEMBL** — All measured activities for a target, curated to one value per compound with units and assay types reconciled.
- **Standardise and deduplicate a library** — Canonical, salt-stripped, deduplicated structures with a log of every change.
- **Similarity screen against known actives** — Library ranked by fingerprint similarity to actives, with an honest check of whether the ranking beats trivial property baselines.
- **QSAR model with a scaffold split** — Property/activity model validated on held-out scaffolds, with an applicability domain and a scrambled-label control.
- **SAR table and matched molecular pairs** — R-group decomposition of a series and the potency change each transformation buys.
- **Map chemical space and pick a diverse subset** — 2D map (UMAP/t-SNE) of a library and a maximally diverse purchase list.

### Drug discovery

- **Dock a library and triage the hits** — Every compound docked into a site, scored, and a shortlist with liabilities named and the score's limits stated.
- **Validate a docking protocol by re-docking** — RMSD of the re-docked co-crystal ligand to its crystal pose before any score is trusted.
- **Prepare a receptor from a crystal structure** — Protonated, repaired receptor with waters/cofactors decided explicitly, ready for docking.
- **Find and rank binding pockets** — Cavities on a protein with volume and druggability descriptors.
- **Protein-ligand interaction fingerprints** — Which H-bonds, salt bridges and contacts each pose makes, compared across a series.
- **Collect every measured compound for a target** — SAR table of all ChEMBL/BindingDB measurements for a target, deduplicated and unit-normalised.
- **Relative binding free energies for a series** — FEP ranking of congeneric ligands with cycle-closure errors. (needs a GPU you connect)
- **Co-fold a target with a ligand** — Complex structure and predicted affinity from Boltz-2 or Chai-1 without a crystal structure. (needs a GPU you connect)
- **Selectivity and off-target profile** — Activity of a series across a target family, and likely off-targets by ligand similarity.
- **Lead-optimisation loop** — Rounds of analogue enumeration, filtering, docking and scoring with the reasoning per round.

### Materials chemistry

- **Is this compound stable? (convex hull)** — Formation energy and energy above the hull against all competing phases, with the phase set's completeness checked.
- **Space group and structure matching** — Space group, Wyckoff positions, standardised cell, and whether two structures are the same material.
- **Elastic constants and moduli** — Elastic tensor, bulk/shear/Young's moduli and mechanical stability criteria.
- **Identify a phase from its XRD pattern** — Simulated powder patterns of candidate phases matched against a measured pattern.
- **ML property model for materials** — Featurised structures (matminer) and a validated model for a target property.

### Molecular dynamics

- **Build and equilibrate a solvated protein** — Solvated, neutralised periodic system from a PDB entry, equilibrated NVT/NPT with convergence checks.
- **Transport properties from equilibrium MD** — Self-diffusion coefficient (with finite-size correction) and viscosity of a liquid.
- **Analyse a trajectory** — RMSD, RMSF, radius of gyration, H-bonds, contacts and RDFs of a supplied trajectory.
- **Production protein MD at microsecond scale** — Long unbiased trajectories of a protein for conformational analysis. (needs a GPU you connect)
- **Free-energy surface by enhanced sampling** — Metadynamics or umbrella sampling along a collective variable, with MBAR/WHAM and convergence evidence.
- **Markov state model from many trajectories** — Metastable states, implied timescales and transition rates.

### Process engineering

- **Design a distillation separation** — Property model choice, VLE curve at column pressure and a sized column (Rmin, stages, feed stage), including refusing a split an azeotrope forbids.
- **Thermodynamic cycle with real-fluid properties** — State points, efficiency and COP of a power or refrigeration cycle.
- **Size a heat exchanger** — Area, pressure drop and rating of a shell-and-tube exchanger for a duty.
- **Reactor with detailed kinetics** — Species/temperature profiles and sensitivity analysis from a published CHEMKIN mechanism.
- **Flame speed and ignition delay against experiment** — Laminar burning velocity and ignition delay vs equivalence ratio, compared with measured data.
- **Regress binary interaction parameters** — Activity-model parameters fitted to VLE measurements, with the fit's residuals.
- **Converge a flowsheet with recycles** — Rigorous column and recycle convergence into a stream table.
- **Techno-economic analysis** — Capital and operating cost, NPV and minimum selling price with a sensitivity tornado.
- **Process dynamics and controller tuning** — Dynamic response of a unit and PID tuning with step tests.

### Quantum chemistry

- **Electronic energy at a stated level of theory** — HF/DFT/MP2 energy of a molecule in named basis sets.
- **Optimise a geometry and confirm the stationary point** — Optimised structure, bond lengths/angles, and a Hessian proving a minimum (0 imaginary) or saddle (exactly 1).
- **Transition state, IRC and barrier** — Located TS, IRC connecting it to both minima, and the barrier.
- **Conformer ensemble with Boltzmann weights** — Conformers generated, optimised (GFN2 then DFT) and Boltzmann-weighted.
- **Non-covalent interaction energy** — Counterpoise-corrected interaction energies benchmarked against S22/S66 references.
- **UV-Vis spectrum by TDDFT** — Vertical excitations and oscillator strengths, broadened into a spectrum.
- **High-accuracy or large-system calculation** — CCSD(T) or large-basis DFT on systems beyond a few dozen atoms. (needs a GPU you connect)

### Reactions and synthesis

- **One retrosynthetic step** — Ranked precursor sets for a target from a template library, with a null-model check.
- **Triage a library by synthesisability** — SA/SC scores and a ranked, filtered list.
- **Yield model from public HTE data** — Yield-prediction model trained on an open high-throughput dataset (e.g. Buchwald-Hartwig), with uncertainty.
- **Design the next batch of condition experiments** — Bayesian-optimisation suggestion of the next conditions to run from results so far.
- **Enumerate a combinatorial library** — Products of building blocks under reaction templates, as a reopenable SDF.
- **Compare routes on green metrics** — PMI, E-factor and atom economy of candidate routes.