f↗foldiffresearch beta
THE RESEARCH PILOT WORKFLOW

Your protein.
Testable hypotheses.
The next experiment series.

Foldiff helps you choose what to test in the laboratory. It compares structures, shows predictions and disagreements, and brings measurement plans and results together.

Try a worked example ↗
01
YOUR QUESTION

Start with a protein and goal

Enter a UniProt accession. For primers, add your full CDS or explore a synthetic gene design. Define application conditions and success criteria for the laboratory series.

02
DATA AND FUNCTION

Find donor candidates

The current beta searches up to 80 reviewed entries with the same EC number, comparing sequences and up to six structures. You can choose a homolog manually. This limited search cannot guarantee the best donor.

Same functionSequence coverageStructure similarity

Temperature and pH information is shown when available in annotations. Similarity and origin from a thermophile alone do not establish the desired stability.

03
STRUCTURE AND LIMITS

Compare and screen functional sites

Retrieve existing AlphaFold DB models and UniProt annotations. Align residues, overlay structures and inspect confidence. Active sites, binding sites and other functional regions are excluded from the main list. Switch between cartoon, surface and sticks, overlay a homolog and highlight differences, deviations or confidence. The legend explains each color.

04
TWO PREDICTORS

Rank with disagreements visible

The linear Foldiff model scores the residue environment and substitution features. The ThermoMPNN neural network adds a second prediction when available. FireProtDB measurements are shown separately with conditions and sources.

Negative ΔΔG suggests stabilization. It cannot be converted into a gain in degrees or activity. Model agreement is not a success probability either.

05
EXPERIMENT SERIES

Select variants and a control

Select candidates, add the WT protein and replicates. Export the series table and primer designs. Distances help reveal contacts between positions; combination effects require separate testing.

06
REAL MEASUREMENTS

Bring experiment results back

Enter measurements or import CSV. The service shows means, replicate spread and differences from WT. Measure activity separately. For pH, view a curve and the maximum among tested points.

07
NEXT SERIES

Distinguish measured candidates from hypotheses

Compare the measured effect and retained activity against your threshold. Show untested variants with agreeing predictions separately. Confirm promising variants in a repeat series. There is no automatic model retraining yet.

Measurement→Repeat testing→Next hypothesis
WHAT THE EVIDENCE SUPPORTS

Evidence is visible.
Accuracy needs testing.

What has been measured

In the saved main-model evaluation, the fraction of stabilizing substitutions among the top twenty was 15% on val, 55% on test and 35% on homologue_free. These describe specific datasets, not your variant’s success probability.

What is still needed

Independent pilots on new proteins, evaluation by family, conditions and construct, numerical prediction errors and comparison against a simple baseline. No validated universal accuracy percentage is claimed.

Current beta limits

Structures are predictions. FireProtDB lookup is not independent of main-model training. Review primers before ordering. A series plan is not a complete laboratory protocol. Means and SD are descriptive statistics; selection criteria do not replace statistical analysis.

Series stay in this browser. Download CSV and JSON; manually restore JSON on another device. Shared accounts, background synchronization and automatic training on client data are not available yet.

Sources: AlphaFold DB, UniProt, FireProtDB, ThermoMPNN.

START A PILOT

One enzyme.
A clear success criterion.

Start with a public protein and worked example. A joint pilot needs a research question, assay conditions, construct and a way to test activity.

Open workspace ↗

What the current version includes

Structure analysis, candidates with evidence, construct designs, experiment tables, measurement analysis and exports.

To discuss a pilot, open @oligoplan_bot. In-app payment and private accounts are not connected yet.