Pressure-Dependent Conformation and Fluctuation in Folded Protein Molecules.

Abstract

Hydrostatic pressure leads to nonuniform compression of proteins. The structural change is on average only about 0.1Åkbar(-1), and is therefore within the range of fluctuations at ambient pressure. The largest changes are around cavities and buried water molecules. Sheets distort much more than helices. Hydrogen bonds compress about 0.012Åkbar(-1), although there is a wide range, including some hydrogen bonds that lengthen. In the presence of ligands and inhibitors, structural changes are smaller. Pressure has little effect on rapid fluctuations, but with larger scale slower motions, pressure increases the population of excited states (if they have smaller overall volume), and slows the fluctuations. In barnase, pressure is shown to be a useful way to characterise fluctuations on the timescale of microseconds, and helps to show that fluctuations in barnase are hierarchical, with the faster fluctuations providing a platform for the slower ones. The excited states populated at high pressure are probably functionally important.