Epistasis/synergy analysis

Epistasis/synergy analysis tool: it first selects the top-N single mutations ranked by the chosen effect direction, then runs the epistatic siamese network on all pairs of these positions, comparing the actual double-mutation ddG with the sum of the two single ddGs to identify synergistic and antagonistic mutation combinations.

The output includes, for each position pair, the single ddGs, additive ddG, epistatic ddG, synergy value (synergy = epistatic - additive) and interaction type. A negative synergy (stabilizing direction) or a positive synergy (destabilizing direction) is marked as synergistic.

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


3. Synergy analysis parameters:

Top-N single mutations: Take the top N single mutations by effect and analyze all pairs (2-50)
Effect direction:
CA-CA distance cutoff: Å Only analyze position pairs with CA-CA distance ≤ this value

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.