Water mediated effects in alpha-helix formation inside nanotubes

We present replica exchange molecular dynamics studies of the phase diagram for alpha-helix formation of capped polyalanine in nanotubes (NT) open to a water reservoir as a function of the NT diameter and hydrophobicity. A helix forms only in a narrow range of diameters. Helix formation in polyalanine is driven by a small negative enthalpy and a positive entropy change at 300 K, in contrast to the large negative entropy change that destabilizes the helix and favors the coiled state in bulk water. To understand the sequence dependence of helix formation inside the NT, solvation thermodynamics are determined by forming a thermodynamic cycle with liquid and gas phase MD simulations. Polyalanine forms a more thermodynamically favorable helix in the presence of water inside carbon and boron nitride NT. This is attributed to a favorable solvent reorganization energy and solvation entropy. In contrast, polyserine forms a stable helix in the gas phase but not in the presence of water while inside the CNT. This is attributed to unfavorable water-mediated interactions. However, polyserine forms a helix in a BNNT inside the gas phase but only over a narrow temperature range in the liquid phase. These data have implications for understanding helix formation inside the ribosome tunnel.