Funnel-like protein energy landscapes emerge from functional evolution under thermal fluctuations

Norifumi Maruyama; Macoto Kikuchi

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arXiv · 2608.01143

Funnel-like protein energy landscapes emerge from functional evolution under thermal fluctuations

Norifumi Maruyama·Macoto Kikuchi

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Abstract

Foldable proteins exhibit funnel-like energy landscapes, but their evolution under selection for function remains unclear. We study this in a lattice protein model, defining fitness as the equilibrium probability of a fixed active-site motif and using multicanonical sequence sampling. At intermediate temperature, rare high-fitness sequences show funnel-like energy and double-well free-energy landscapes. At very low temperature, abundant high-fitness sequences retain glass-like landscapes. Thus, thermal fluctuations turn a local functional requirement into a global structural constraint.

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Norifumi Maruyama, Macoto Kikuchi. 2026-08-02. Funnel-like protein energy landscapes emerge from functional evolution under thermal fluctuations. https://arxiv.org/abs/2608.01143

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