Folding of α-helices into bundles in long polyalanines

The conformational structure of unsolvated polyalanine molecules (Ala)n is explored in a wide range of chain lengths n by MD simulations using the Amber force fields. Remarkably, on cooling long Ala peptides to 303 K the straight α-helix is fragmented into shorter pieces that organize into helical bundles. The straight α-helix becomes unstable in polypeptides of the length over n ∼ 55. Several bundles differing in the number of helical fragments coexist in a molecule of a given chain length. Antiparallel helices, connected by short coils, are stabilized in a bundle by short-range attraction and packed roughly in a 2D-hexagonal lattice. The computed average length of helices in bundles, of about 28 residues, excellently matches the data for the span of transmembrane protein helices. The transition of a straight helix into helical bundles in long unsolvated polypeptides detected in simulation is supported by the existing experimental data on the Ala peptides in the gas phase. The stabilization energy of bundles estimated by two complementary approaches favors the two-helix and seven-helix arrangements.