Helix formation inside a nanotube: possible influence of backbone-water hydrogen bonding by the confining surface...

Recent molecular dynamics simulations of Sorin and Pande [J. Am. Chem. Soc. 128, 6316 (2006)] in explicit solvent found that helix formation of an alanine peptide is disfavored inside a nanotube relative to that in bulk solution. Here, we present a theory to quantitatively rationalize their simulation results. The basic idea is that the nonpolar inner surface of the nanotube creates a depletion layer and raises the activity of the confined water. The raised water activity, in turn, stabilizes the coil state through hydrogen bonding with the backbone amides and carbonyls. We account for the influence of water activity on helix formation within the Lifson-Roig theory. With physically reasonable parameters, the dependence of the helical content on the diameter of the nanotube obtained in the simulations is well reproduced.