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Energetic frustration can be reduced with the appropriate design for the protein sequence.
Based on our simulation, we estimate the residual energetic frustration of λ6 85 to be δ2 G ≈ 0.64 k2T2.
Recent studies indicate that an addition of a small amount of energetic frustration may enhance folding speed for certain proteins.
We designed a protein with this property by reducing the energetic frustration in the original α/β sandwich substrate protein.
The folding rate increases due to reduced-dimension pathways arising from the mere presence of intermediate states, but decreases if the contacts in the intermediate are very stable and introduce sizeable topological or energetic frustration that needs to be overcome.
We show that λ6 86, as well as very fast folding proteins or folding intermediates estimated to lie near the speed limit, provide a better rate-topology correlation than proteins with larger energetic frustration.
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