  In contrast to the well-known destabilization of globular proteins by high
pressure, re- cent work has shown that pressure stabilizes the formation of
isolated {\alpha}-helices. However all simulations to date have obtained a
qualitatively opposite result within the experimen- tal pressure range. We show
that using a protein force field (Amber03w) parametrized in conjunction with an
accurate water model (TIP4P/2005) recovers the correct pressure- dependence and
an overall stability diagram for helix formation similar to that from experi-
ment; on the other hand, we confirm that using TIP3P water results in a very
weak pressure destabilization of helices. By carefully analyzing the
contributing factors, we show that this is not merely a consequence of
different peptide conformations sampled using TIP3P. Rather, there is a
critical role for the solvent itself in determining the dependence of total
system volume (peptide and solvent) on helix content. Helical peptide
structures exclude a smaller volume to water, relative to non-helical
structures with both the water models, but the total system volume for helical
conformations is higher than non-helical conformations with TIP3P water at low
to intermediate pressures, in contrast to TIP4P/2005 water. Our results further
emphasize the importance of using an accurate water model to study protein
folding under conditions away from standard temperature and pressure.
