Non‑Equilibrium Monte Carlo Simulations of Protein Folding

Protein folding is usually treated as a random search driven by thermal agitation, with the environment modeled as a heat bath that delivers uncorrelated kicks, white noise, flat and memoryless. But the inside of a cell is nothing like that. It’s crowded, sticky, viscoelastic. A thermal fluctuation doesn’t fade instantly; it lingers, subtly shaping the next one. This study set out to see what happens when the noise remembers. We simulated a small ۲۰‑mer hydrophobic‑polar lattice protein using Monte Carlo, but replaced the usual white‑noise thermostat with something more lifelike. The effective temperature followed an Ornstein‑Uhlenbeck process, its fluctuations correlated over a tunable timescale; Not too fast. Not too slow. Just enough for each thermal kick to carry a trace of the last. The results were striking. Even modest memory, already pushed folding performance past the white‑noise baseline. At intermediate correlation times, the protein explored a wider range of conformations and formed native contacts more reliably. But when the memory stretched too far, past, the chain got stuck. It settled into misfolded arrangements and couldn’t escape. What emerges is a kind of resonance. Not too random, not too persistent. A sweet spot where environmental memory actually aids the search for the native state. The cytoplasm’s viscoelastic chatter, then, may not be just noise to filter out. Under the right conditions, it becomes part of the folding machinery itself.

کلیدواژه ها:

Protein folding ، Ornstein–Uhlenbeck process ، Monte Carlo simulation ، Non‑equilibrium thermodynamics