We study cold denaturation of proteins at high pressures. Using multicanonical Monte Carlo simulations of a model protein in a water bath, we investigate the effect of water density fluctuations on protein stability. We find that above the pressure where water freezes to the dense ice phase ([Formula presented]) the mechanism for cold denaturation with decreasing temperature is the loss of local low-density water structure. We find our results in agreement with data of bovine pancreatic ribonuclease [Formula presented].

Original languageEnglish (US)
JournalPhysical review letters
Issue number13
StatePublished - 2003

All Science Journal Classification (ASJC) codes

  • General Physics and Astronomy


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