UNICORNE Documentation

A guide to using the Unified Conformational Ensemble database for exploring multiconformational protein structures.

1. View Modes

UNICORNE offers two ways to browse protein structures:

UniProt View (default)

A flat list of all UniProt entries. Each entry contains the aligned monomeric and oligomeric structure ensembles that map to that UniProt ID. Best for exploring a specific protein.

Fold/Domain View

Structures organized by fold and domain classifications. Navigate through Fold → Domain → UniProt → Structures. Best for exploring structural relationships across protein families.

Switch between views using the UniProt and Fold/Domain buttons at the top of the sidebar.

2. Searching

Type in the search bar and press Enter to search. You can search by:

• UniProt ID — e.g., P00323
• Entry name — e.g., FLAV_NITV2
• Protein name — e.g., Flavodoxin
• Structure ID — e.g., 1AKQ

In Fold/Domain view, you can also search by fold name or domain name.

3. Filters

Click the filter icon button to open the filter panel. Filters differ between views. Set your desired range, then press Enter or search to apply.

UniProt View Filters

• Conformations — Number of available structure conformations
• Min-TM Score — The minimum pairwise TM-score among all aligned structures (0–1). Lower values indicate greater structural diversity.
• Protein Length — Number of amino acid residues
• Avg Coverage — Average fraction of the sequence covered by aligned structures (0–1)

Fold/Domain View Filters

• Total Avg Angle — Average principal angle across all pairwise comparisons within the fold (degrees)
• Avg Seq Similarity — Average pairwise sequence identity among proteins in the fold (0–1)
• Direct UniProts — Number of UniProt entries directly assigned to the fold

All filters are double-sided range sliders. You can drag the endpoints or type exact values into the number fields.

4. UniProt Entries

Click on a UniProt entry to expand it. Inside each entry you will see:

• Entry Name and Protein Name — from the UniProt database
• Select All — Checks all structure checkboxes and starts the NMD animation in the normal mode viewer
• Clear — Unchecks all structures for this UniProt
• Share — Copies a direct URL to this UniProt entry to your clipboard
• Structure checkboxes — Check individual structures to load them. Clicking a checkbox loads the NMD animation for that UniProt in the normal mode viewer.

5. Normal Mode Viewer (Upper Panel)

Displays a single protein structure animated along its principal modes of conformational variation (PCA-based normal mode dynamics). Both 3D viewers are powered by Mol*.

Animation

• Play (▶) — The play button in the viewport toolbar animates the structure back and forth along the selected mode. Press again to pause.
• Mode selector — The dropdown at the top-left of the viewer chooses which principal component mode to animate. Each entry lists the mode's peak displacement in angstroms and the fraction of total variance it explains (e.g., “Mode 1 · 2.76 Å · 80.8%”). The animation amplitude matches the mode's √λ scaling, so higher-variance modes move further.

Displacement Colouring

By default the structure is coloured by per-residue displacement (RMSF): blue marks the most stable residues and red the most mobile, with the legend scaled in angstroms (Å) for the current mode. This displacement colouring stays the default even when you switch representation from the controls panel; you can still choose any other Mol* colour theme (rainbow by sequence position, secondary structure, by chain, …).

Displacement Vectors

Click the arrow button (↗) in the viewport toolbar to toggle displacement vectors — cone-tipped arrows drawn from each residue showing the direction and magnitude of motion for the current mode. The button highlights teal while vectors are shown. Vectors follow the selected mode and clear automatically when you load a different protein.

Representation & Settings

Open the controls panel (the Toggle Controls Panel button in the viewport toolbar) to change the representation (cartoon, molecular surface, ball & stick, putty, …) and colour theme. The toolbar also provides reset view, screenshot, fullscreen, and Mol*'s settings (including background colour).

Hover

Hover over any residue to highlight it and show an info label with the chain, residue name, and residue number.

6. Superposition Viewer (Lower Panel)

Overlays multiple selected structures for visual comparison, also rendered with Mol*. Structures load automatically as you check them — there is no separate Visualize button. Unchecking a structure hides it without reloading the others.

Appearance

• Each structure is drawn as a cartoon in its own colour; a colour legend in the corner of the viewer maps colours to structures.
• Use the controls panel to change the representation or colour theme — e.g., rainbow (by sequence position), secondary structure (helix / sheet / coil), or by chain.
• Show 2 furthest (min TM) — a button in the stats sidebar loads only the two structures with the lowest pairwise TM-score (the greatest structural difference).

Hover

Hover over any residue to see an info label; the structure's PDB ID is included so the overlaid models can be told apart.

Fullscreen

Use the fullscreen button in the viewport toolbar to expand either viewer.

7. Sequence Panel

When at least one structure is loaded into the superposition viewer, a Sequence panel appears at the bottom of the right sidebar. It lists each loaded structure's sequence, aligned by residue number so the same column corresponds to the same UniProt position across all superposed structures.

• Each row is labeled with the structure ID in its model colour; gaps where a structure does not cover a residue show as ·.
• Sequence wraps in fixed-width blocks that match the panel's current width — resize the sidebar to see more or fewer residues per line.

8. Resizable Layout

Both sidebars are draggable. Hover over the divider between the protein list and the viewer area, or between the viewer area and the stats sidebar — the cursor will change to a resize cursor. Drag to set your preferred widths.

• The 3D viewers automatically resize as you drag, so the structure stays centered without clipping.
• The sequence panel re-flows its blocks to fit the new sidebar width.
• Widths are saved in your browser's local storage and persist across reloads.
• Keyboard: focus the divider with Tab and use ←/→ to nudge by 16 px at a time.

9. Statistics Panels

Statistics appear in the right sidebar when you select a UniProt, fold, or domain. Click the ⓘ button next to any statistic for a detailed explanation.

UniProt Statistics (flat view)

• Length — Number of amino acid residues
• Avg Coverage — Average fraction of the sequence covered by aligned structures
• Max GLOCON Score — Highest principal angle, indicating maximum conformational diversity
• Max GLOCON IDs — The two structures with the maximum principal angle difference
• Min TM Score — Lowest pairwise TM-score (greatest structural divergence)
• Min TM IDs — The two structures with the minimum TM-score

Fold Statistics (Fold/Domain view)

• Total Average — Average principal angle across all pairwise comparisons
• Min Average — Most conformationally conserved UniProt
• Avg Min — Average of each UniProt's minimum principal angle
• Min Min — Lowest principal angle observed in the fold
• Avg Seq Similarity — Average pairwise sequence identity

Domain Statistics (Fold/Domain view)

• Total Average — Average principal angle within the domain group
• Min Average — Most conformationally conserved UniProt in the domain
• Avg Min — Average of each UniProt's minimum principal angle
• Min Min — Lowest principal angle in the domain

10. Global Controls

• Download PDBs — Downloads all checked structures as individual PDB files
• Select All — Checks all visible structure checkboxes
• Clear All — Unchecks everything, stops animations, clears both viewers, and resets the Show dropdown
• Theme Toggle — Switch between dark mode (default) and light mode. Your preference is saved.
• Leaderboard — Opens the UNICORNE_BENCH structure-prediction leaderboard (see section 12).

11. Icons & Indicators

• ▶ Play — Appears next to UniProt entries that have normal mode animation data available. In Fold/Domain view, play icons reflect availability for that specific fold context.
• Conformation count — Shown as (N confs) next to each UniProt, indicating the number of displayable structure conformations.
• Green dot — Status indicator at the bottom of the page showing the application is connected and data is loaded.

12. Benchmark Leaderboard

The leaderboard at /leaderboard evaluates structure-prediction tools on two benchmark datasets:

• UNICORNE_BENCH — 854 protein ensembles, each with multiple experimentally-determined ground-truth conformations. The headline benchmark.
• UNICORNE_OC24 — A curated 24-protein subset, each with 2–5 representative GT conformations drawn from a complete-linkage clustering of available PDB structures (see benchmarking-dataset-OC24-complete-linkage.csv). Smaller, faster to iterate against, used for focused method development.

The Dataset dropdown switches between them. The same tools are scored on both: alphaflow_pdb, afsample2, bioemu, cfrandom, esmdiff, esmflow_pdb, speach_af.

The table

Each row is one ensemble; each tool column shows the mean of the per-GT best TM-score — for every ground-truth conformation, the closest predicted structure's TM is taken, and those values are averaged. Higher is better. Click a column header to sort. Use the search bar to filter by UniProt ID or protein name.

• GT — Number of ground-truth conformations in the ensemble.
• len — Reference sequence length.
• Pair TM — Minimum pairwise TM among the GT conformations. Lower means the ensemble is more conformationally diverse, which makes it harder to predict.
• Per-tool columns — Mean of best-per-GT TM. Color-coded green (≥ 0.8), amber (0.6–0.8), red (< 0.6).

Graph view

Toggle to Graph for a scatter plot of min pairwise TM across GT conformations (x — ensemble diversity) vs. worst-GT best-pred TM (y — tool score on the hardest conformation). Each point is one ensemble; one trace per tool. Click any point to load that ensemble's viewer. Filter by AF2 training-cutoff status (in / out / all) to compare tools on truly out-of-distribution targets.

3D viewer

Click a row (or graph point) to open the superposition viewer (rendered with Mol*). The viewer has two modes:

• GTs — Superpose every ground-truth conformation in the ensemble in grayscale. Toggle individual GTs on / off in the legend.
• Pred — Compare predictions against the ground truth. GT chips at the top act as multi-select toggles: clicking adds (or removes) that GT from the superposition; the most-recently-clicked GT is "active" and gets an outer outline. Each visible tool's best prediction for every selected GT is overlaid at the active opacity (slider) and in its tool color.

• Pred opacity slider controls the prediction transparency.
• Settings (gear icon) — Choose Color scheme (Per-tool, Rainbow, Secondary structure), Background, and Reset zoom.
• Fullscreen (⛶) and double-click on the viewer toggle fullscreen.

Metrics + Sequence

Below the viewer: a metrics table lists each tool's TM against the active GT, the full tool×tool pairwise-TM matrix at that GT (i.e., TM between every pair of tools' best-pred structures), and RMSD. The header reads Pairwise TM at GT: <name> — in Pred mode when multiple GTs are selected, this matrix follows the last-selected GT, so you always know which conformation the numbers correspond to. Eye toggles per row hide / show individual tools in the viewer. To the right of the viewer, the reference vs. GT-chain sequence alignment with mismatches in lowercase — hover any residue to highlight it in the alignment.

The inter-tool TM values come from data/inputs/<dataset>/<tool>-inter-tool-TM-scores.csv: one CSV per tool, one row per (uniprot, GT_conf), columns being the other six tools' TM-scores. Values are max(TM_chain1, TM_chain2, TM_avg) from a single TMalign call per pair.

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UNICORNE — MIT License — Affiliation withheld for double-blind review