Comprehensive and accurate Ab initio energy surface of simple alanine peptides

Secondary structures for AcAla(n)NH(2) (n=2-4) peptides have been analyzed by means of ab initio MP2, CCSD(T), and DFT-B3PW91 methods using large basis sets and including implicit hydration effects and thermal corrections. In addition to the classical "pure" right-handed 3(10)- and α-helices, left-handed polyproline II, inverse γ-turn, and fully extended conformations, a large number of "mixed" structures obtained by combining characteristic φ/ψ angles of each residue in every way have been found. All mixed structures are energetically accessible and can be present at significant levels in aqueous solution. Furthermore, they represent the way through which hierarchical unfolding of 3(10)- and α-helices or nonhierarchical polyproline II to fully extended transitions occur. Computational results are in qualitative agreement with the large amount of experimental data for simpler polyalanines and provide significant insight into their thermodynamic properties and how these can be modulated by interactions with solvent.