Protein Mutation ΔΔG Calculator

Mutation ΔΔG prediction tool: given one or more specified mutations, it directly returns the model-predicted ddG values (kcal/mol) without performing a full sequence scan. Single mutations (e.g. 10V) and double mutations (e.g. 10V:12W, two positions joined by a colon) are supported.

Mutation numbering uses chain + PDB residue numbering (1-based) semantics: first select the target chain below, then enter the PDB residue number and the mutant amino acid on that chain; the wild-type amino acid is read automatically from the structure file. Double mutations can be computed by additivity (sum of the two single ddGs, fast) or exactly (epistatic siamese network, more accurate but slower).

1. Upload protein structure file (PDB / mmCIF):

3. Mutation query settings:

Mutations:		Format: PDB residue number + mutant amino acid, e.g. 10V. Double mutations join two positions with a colon, e.g. 10V:12W. Single and double mutations cannot be mixed.
Double mutation method:	Additive (fast) Exact (epistatic)	Only applies to double mutations; the exact mode is slower

References

Dieckhaus H, Kuhlman B. Protein stability models fail to capture epistatic interactions of double point mutations. Protein Sci. 2025 Jan;34(1):e70003. doi: 10.1002/pro.70003. PMID: 39704075; PMCID: PMC11659742.