Fast-folding proteins under stress

Proteins are subject to a variety of stresses in biological organisms, including pressure and temperature, which are the easiest stresses to simulate by molecular dynamics. We discuss the effect of pressure and thermal stress on very-fast-folding model proteins, whose in vitro folding can be fully simulated on computers and compared with experiments. We then discuss experiments that can be used to subject proteins to low- and higherature unfolding, as well as low- and high-pressure unfolding. Pressure and temperature are prototypical perturbations that illustrate how close many proteins are to instability, a property that cells can exploit to control protein function. We conclude by reviewing some recent in-cell experiments, and progress being made in simulating and measuring protein stability and function inside live cells.