DocsScienceFold & Studio

Fold & Studio

Two workspaces for protein structures, next to the Workbench. Fold predicts a structure from a sequence and lets you question it. Studio keeps a structure as a project, with labels, figures and a stack of edits you can switch on and off.

01Fold

Paste an amino-acid sequence, between 8 and 400 residues. Fold predicts its structure with ESMFold and shows it in 3D, coloured by per-residue confidence (pLDDT). A nucleotide sequence is recognised and refused with an explanation.

Before it explains the structure, Fold tries to identify the protein by exact sequence match against UniProt. When the sequence is a known protein, the explanation leads with its real name. Without an exact match, it explains the structure from the sequence alone.

After a fold the page splits in two: the structure on the left, a chat on the right that explains what you are looking at.

Fold does not save anything. Labels last for the session. To keep an annotated structure, use Studio.

02Studio

Studio is a dashboard of protein projects. Each project holds one structure, the labels pinned to it, a conversation about it, and the figures you save from it. Each project has its own link, and projects can be cloned and deleted.

Starting a project

Start fromWhat happens
PDB entryAn experimental structure fetched from the RCSB PDB by its four-character ID, with its method and resolution.
UniProt accessionThe AlphaFold DB model for that accession, coloured by per-residue confidence.
Amino-acid sequenceA sequence or FASTA record, folded with ESMFold (up to 400 residues). It is identified first where possible.
Upload a fileA .pdb, .cif, .ent or .fasta file. Coordinates are parsed without sending the file to an outside service.
Describe what it doesA plain description, such as "an enzyme that cuts DNA". Studio finds the closest real protein and loads its structure. If nothing matches exactly, you get the closest match and it says so.
Start emptyA blank viewer and chat. Ask the assistant for a protein.

Labels from measured features

When a structure loads, Studio measures it: secondary structure, buried and exposed residues, cavities, disulfides, metal sites, salt bridges, catalytic triads and common sequence motifs. Where a ligand is bound, its contact shell is the binding site.

Requests like "label the active site", "label the cysteines" or "label helix 3" are resolved against those measured features first, with no model involved. A model is consulted only when that finds nothing, and even then it can only choose from features that exist in the structure. Every label is pinned to a real residue.

Tweaks: editing a protein

Tweaks are edits stacked on top of the original structure. The original is never changed, so every edit can be switched off, reordered or removed, and you always have a wild-type to compare against.

EditHow the structure is updated
SubstitutionSide chains rebuilt in place on the existing backbone.
Deletion, truncationAtoms removed from the existing coordinates.
Disulfide stapleExactly two residues made cysteines to form a new disulfide, on the existing backbone.
Insertion, tagThese change the backbone, so the construct is refolded from its sequence and renumbered.

Tags include His6, His8, FLAG, Myc, Strep-II, HA, a TEV site, a sortase motif, and flexible and rigid linkers. A project can hold up to 60 tweaks.

Common requests such as "mutate Ser195 to alanine" are parsed by rule and cannot target a residue that does not exist. Open-ended requests such as "make it more soluble" go to a model, which is given the measured features and whose suggestions are checked against the real residues. Suggestions arrive as cards to accept or discard; nothing is applied until you accept it.

Labels are anchored to residues, not positions. When an edit renumbers the chain, labels follow their residues. A label on a residue that an edit removed says so instead of moving to a neighbour.

What a tweak is likely to do

Each tweak gets three readings, built from features measured on the structure:

PanelWhat it is
StabilityA banded estimate, from stabilising to likely disruptive, with every contributing term listed. Never a kcal/mol figure.
Functional-site impactWhether the edit touches a measured site. A lookup, not a prediction.
DevelopabilityLiabilities found by exact sequence and structure rules, such as a new deamidation motif.
NoteThe stability band is a transparent heuristic. It is tuned so well-known mutations come out in the right order and band. It is not a measurement of free energy.

Exporting

From a project you can download the view as a PNG with its labels, save it as a figure in the project, or export the current construct as FASTA, as PDB, or as a plain-text report of the tweak stack.

03Structures in the Workbench

The Workbench agent builds interactive 3D models too, from a PDB id, a UniProt accession, a sequence or inline coordinates, and it can find binding sites and dock molecules. Those models appear in the chat and in Artifacts. See Figures, models and artifacts and Engines & discovery.

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