Protein Engineering

Stability Prediction.FoldX Integration.
Physics-Based Stability Prediction.

Quantitative assessment of mutation impact on protein stability using empirical force field calculationsFoldX empirical force field calculations. Predict destabilizing variants, guide protein engineering, and assess drug resistance mechanisms.

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Thermodynamic Engine

ddG CalculationsFoldX ddG Calculations

Our engine usesFoldX uses an empirical force field to estimate the free energy change upon mutation. Negative ddG indicates stabilization; positive ddG indicates destabilization.

ΔΔG = ΔGmut − ΔGwt
ΔΔGChange in folding free energy upon mutation (kcal/mol)
ΔGmutFolding free energy of the mutant structure
ΔGwtFolding free energy of the wild-type structure
< 0Stabilizing mutation — improved folding
−0.5 to 0.5Neutral — within noise threshold
> 0Destabilizing mutation — reduced folding

Energy Decomposition

The engine evaluatesFoldX evaluates 9 energy terms for each mutation:

Van der WaalsEvdw
Solvation (hydrophobic)EsolH
Solvation (polar)EsolP
Hydrogen bondsEhb
ElectrostaticsEel
Backbone entropySmc
Side-chain entropySsc
Torsional clashesEclash
Covalent bondsEcov
Mutation Assessment

Mutation Impact Visualization

Example stability predictions from our stability engineFoldX engine. Color-coded by thermodynamic impact on protein folding stability.

MutationPositionddG (kcal/mol)ImpactConfidenceClassification
A42GCore-1.84 Stabilizing0.94Improved packing
V87LCore-0.92 Stabilizing0.88Enhanced VdW
T65SSurface0.12 Neutral0.91Solvent-exposed
K103NInterface-0.31 Neutral0.85H-bond compensated
G156DLoop+2.47 Destabilizing0.92Steric clash
P203LCore+4.13 Destabilizing0.96Proline backbone break
W254FCore+1.68 Destabilizing0.89Lost aromatic stacking
Production Engine

20,924 Lines of Production Code

Battle-tested across hundreds of protein engineering projects. Built for reliability, speed, and regulatory-grade reproducibility.

20,924
Lines of Code
9
Energy Terms
0.46
kcal/mol RMSE
<30s
Per Mutation
Applications

Use Cases

Physics-based stability analysisFoldX stability analysis powers decisions across protein engineering, clinical genomics, and drug development.

Protein Engineering

Systematically scan all single-point mutations to identify stabilizing variants for improved expression, thermal tolerance, and shelf life. Guide directed evolution campaigns.

Variant Assessment

Evaluate clinical variants of unknown significance (VUS) by predicting their impact on protein stability. Prioritize pathogenic candidates for experimental validation.

Drug Resistance Prediction

Model how mutations in viral or bacterial proteins affect drug binding. Predict resistance-conferring mutations before they emerge clinically.

Predict Stability Before the Bench

Identify stabilizing mutations, assess pathogenic variants, and model drug resistance with physics-based precision.

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