Analyzer Module

The analyzer module (pharmacon.analyzer) is the computational core of Pharmacon. It contains all analysis algorithms as standalone, stateless routines that operate on MDAnalysis selections and return raw numerical results.

RMSD

Computes the Root Mean Square Deviation of atomic positions relative to a reference frame. Supports multiple atom-group selections per run with a dedicated fitting group for structural alignment. Results are stored per-frame in the .pta file and plotted as time series.

CLI: pharmacon trajectory rmsd

RMSF

Computes the per-atom Root Mean Square Fluctuation, i.e. the time-averaged positional fluctuation of each atom about its mean position. Supports multiple atom-group selections per run with a dedicated fitting group for in-memory structural alignment. Alignment defaults to a two-pass scheme (align to the initial frame, build the average structure, then re-align to it) and can optionally target a single reference frame. Per-selection RMSF values plus aggregate statistics are stored in the .pta file and plotted as RMSF profiles.

CLI: pharmacon trajectory rmsf

Distances

Computes pairwise or group-to-group distance time series between user-defined atom selections. Four computation modes are supported:

  • MIN — minimum distance between any atom pair across the two groups

  • MAX — maximum distance between any atom pair across the two groups

  • COM — distance between the centres of mass

  • COG — distance between the centres of geometry

All calculations are PBC-aware. Multiple distance pairs can be calculated in a single run.

CLI: pharmacon trajectory distances

Angles

Measures geometric angles across a trajectory. Three angle types are supported, selected by the format of the MDAnalysis selection string:

Type

Selection syntax

Example

Three-atom angle

Select exactly 3 atoms; angle is measured at the central atom

"index 10 or index 11 or index 12"

Vector angle

Two atom pairs separated by ->

"index 10 or index 100 -> index 300 or index 301"

Dihedral / torsion

Select exactly 4 atoms; torsion measured around the central bond

"index 10 or index 11 or index 12 or index 13"

All calculations are PBC-aware when box dimensions are available.

CLI: pharmacon trajectory angles

Non-Covalent Interactions

Detects and quantifies nine types of non-covalent interactions on a per-frame basis. Atom-type classification uses RDKit SMARTS pattern matching for accuracy. Available for both protein–ligand and protein–protein pairs.

Interaction

Detection criterion

Hydrophobic contacts

Distance-based between non-polar atoms

Hydrogen bonds

Donor–hydrogen–acceptor geometry: distance + D–H···A angle

Ionic / salt-bridge

Oppositely charged groups within a distance cutoff

Halogen bonds

C–X···A geometry with angle validation

Metal contacts

Metal ion coordination to nearby electronegative atoms

Water bridges (1st degree)

Single bridging water mediating an H-bond chain between two groups

Water bridges (2nd degree)

Two bridging waters forming an extended H-bond network (not yet implemented)

Pi–cation

Aromatic ring to charged group: distance + angle threshold

Pi–stacking

Parallel or T-shaped aromatic ring pairs classified by geometry

Each interaction record includes:

  • Full atom metadata for both partners (name, residue, chain, segment)

  • Interaction-specific geometric details (distances, angles, orientation)

See Interaction row schema in File Formats for the full column schema.

CLI: pharmacon trajectory pl-interactions / pharmacon trajectory pp-interactions

Hydrogen Bonds (standalone)

Dedicated hydrogen-bond analysis that can be run independently from the full interaction profiler. Uses the same donor–acceptor detection and geometric criteria but produces a focused output containing only hydrogen-bond records. Useful when the hydrogen-bonding network is the sole interest.

CLI: pharmacon trajectory h-bonds

Principal Component Analysis (PCA)

Performs PCA on atomic coordinates across a trajectory to identify dominant modes of conformational motion.

Outputs stored in the .pta file:

  • Eigenvalues (explained variance ratios)

  • Eigenvectors (principal components)

  • Per-frame projections onto each selected component

Plot types produced by pharmacon plot pta:

  • PC projections vs time (time series)

  • PC1 vs PC2 scatter plot

  • Variance-ratio scree plot

  • Free-energy surface (FES) heatmap

  • Probability density heatmap

CLI: pharmacon trajectory pca

Average Structure

Computes per-atom mean coordinates over a specified frame range of a trajectory, with optional alignment to a reference frame. The resulting average structure is written as a coordinate file for visualisation or further analysis.

CLI: pharmacon trajectory average-st

Sequence Extraction

Extracts amino-acid sequences from a topology file, organised by chain.

Outputs:

  • Single-letter sequence (aa1_seq)

  • Three-letter residue list (aa3_list)

  • Residue ID mapping (resid_seq)

Supports FASTA export via pharmacon export psa -f fasta.

CLI: pharmacon structure sequence

Molecular Properties

Computes structural and chemical descriptors for small molecules using RDKit.

Scalar properties:

  • Molecular weight, LogP, TPSA

  • Rotatable bond count, ring count, aromaticity flags

  • Stereocenter count, net formal charge

  • Element composition, molecular volume, fragment counts

Fingerprints:

  • Morgan / ECFP (circular fingerprint)

  • Topological torsion

  • Atom pair

  • MACCS keys

Results support CSV export and ML-ready parquet fingerprint dumps.

CLI: pharmacon structure properties