Thermodynamics of Helix-Coil Transitions of Polyalanine in Open Carbon Nanotubes

Understanding structure formation in polypeptide chains and synthetic polymers encapsulated in pores is important in biology and nanotechnology. We present replica exchange molecular dynamics studies of the phase diagram for α-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, which surprisingly is comparable to the width of the ribosome tunnel. Increasing the hydrophobicity enhances helicity in the NT. 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. There is an anticorrelation between water density inside the nanotube and structure formation. Confinement-induced helix formation depends on amino acid sequence. There is complete absence of helix in polyglutamine and polyserine confined to a open carbon nanotube.