α- and 3₁₀-Helix Interconversion:  A Quantum-Chemical Study on Polyalanine Systems in the Gas Phase and in Aqueous Solvent

Abstract

Helices are among the predominant secondary structures in globular proteins. About 90% of the residues in them are found to be in the alpha-helical conformation, and another 10% in the 3(10) conformation. There is a standing controversy between experimental and some theoretical results, and controversy among theoretical results concerning the predominance of each conformation, in particular, helices. We address this controversy by ab initio Hartree-Fock and density functional theory studies of helices with different lengths in a vacuum and in the aqueous phase. Our results show that (1) in a vacuum, all oligo(Ala) helices of 4-10 residues adopt the 3(10) - conformation; (2) in aqueous solution, the 6-10 residue peptides adopt the alpha-helical conformation; (3) there might be two intermediates between these helical conformers allowing for their interconversion. The relevance of these results to the structure and folding of proteins is discussed.

Efficient model chemistries for peptides. I. General framework and a study of the heterolevel approximation in RHF and MP2 with Pople split‐valence basis sets

“…2 ), < t / point > (hours) that 6-31++G(d) is as efficient as the most efficient basis sets of the rules-complying group (being outperformed only by some of the ones in the third group in table 2), that 6-31 · +G(d,p) has drifted a little towards the inefficiency region and that that 6-31++G( · ,p) is well deep in it. This suggests that it may be profitable to break rule (ii) but only in the direction of removing shells from the hydrogens, and not from the 1st-row atoms; in agreement with the common practice in the literature [6,16,20,22,27,29,31,32,93,97] based on the intuition that 'hydrogens are typically more passive atoms sitting at the end of bonds' [56]. On the other hand, 6-31G(f,d) turns out to be very inefficient, being about as accurate as the simple 6-31G basis set but far more expensive.…”

“…• The 6-31G(d) basis set, which is frequently used in the literature, [8,9,12,15,16,29,97,101,111,115,116], has turned out to be a very efficient one for calculating the geometry both at RHF and MP2.…”

Secondary structures of short peptide chains in the gas phase: Double resonance spectroscopy of protected dipeptides

“…For the protected dipeptides Ac-Phe-Pro-NH 2 and Ac-Pro-Phe-NH 2 , we recently reported the observation of a double ␥-fold as well as a specific type of ␤-turn with the Pro amide bond in a cis conformation. 35 The present paper provides evidence for the spontaneous formation of secondary structures in the gas phase, namely, ␤-turns and 2 7 ribbons, and demonstrates a sequencedependent competition between these forms. As model systems, we choose a series of protected dipeptides: Ac-Xxx-Phe-NH 2 , XxxϭGly ͑glycine͒, Ala, and Val ͑va-line͒.…”

“…Over the last years, numerous groups have thus studied unsolvated model peptide chains of increasing size using various levels of theory. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] In a few cases, structures of small peptides protected on both their C and N termini, have been studied in order to investigate the competition between different protein secondary structures, such as ␤-turns, ␤-strands, and ␣ or 3 10 helices. 1,3,6,[12][13][14][15] Computational studies could not be easily compared to experimental investigations, which have been carried out so far in condensed phases.…”

“…35 Even in a protected peptide containing only two residues, several secondary structures can be expected, either based upon a succession of local conformational preferences ͑such as the 2 7 ribbons, which correspond to a daisy chain of C 7 ␥-folds, or like the ␤-strands corresponding to a fully extended backbone, stabilized by a weak C 5 interaction͒, or based upon the formation of H-bonds between more remote NH and CO sites along the backbone ͑such as the ␤-turns, stabilized by C 10 bonds͒. For the protected dipeptides Ac-Phe-Pro-NH 2 and Ac-Pro-Phe-NH 2 , we recently reported the observation of a double ␥-fold as well as a specific type of ␤-turn with the Pro amide bond in a cis conformation.…”