Comprehensive and Accurate Ab Initio Energy Surface of Simple Alanine Peptides

Abstract

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.

Highly Efficient and Chemoselective Zinc‐Catalyzed Hydrosilylation of Esters under Mild Conditions

“…In recent publications on AcAla n NH 2 peptides, by means of high‐level quantum chemical calculations, we showed a strong coupling between peptidic and solvent dipoles; thus, PPII and 3 10 helix do not exist as stable structures in the gas phase, whereas minima were found once implicit solvent effects were considered 29. 30 Despite the absence of explicit water molecule coordination, the computed Δ G 298 values of pure and mixed FE/PPII conformations are reasonably close to experimental values, whereas related computed Δ H and Δ S trends are similar, but they quantitatively deviate from those experimentally derived.…”

Interfacial water at the trialanine hydrophilic surface: a DFT electronic structure and bottom-up investigation

“…27,35 Nevertheless, to test the robustness of present results selected calculations have been performed using other type of DFT, specifically the pure TPSS-TPSS and the hybrid B3LYP and B3PW91 including Grimme-D3 dispersion terms ( Table 1). 27,35 Nevertheless, to test the robustness of present results selected calculations have been performed using other type of DFT, specifically the pure TPSS-TPSS and the hybrid B3LYP and B3PW91 including Grimme-D3 dispersion terms ( Table 1).…”

“…However, the slow dynamics at the interface is in part due to the strong peptide-water hydrogenbonds but also to the heterogeneity of the peptide surface that largely disrupts the water-water synergistic reorientation mechanisms. 27 With the aim of getting computational data that are as free as possible from empirical assumptions and hence able to provide complementary and independent information to the scientific community, there has recently been a flourishing of quantum chemical studies on the solvation effects upon peptide properties. For example, short alanine based peptides adopt compact structures with strong intramolecular H-bonds in the gas-phase [22][23][24][25] or apolar solutions.…”

Local Order in the Unfolded State: Conformational Biases and Nearest Neighbor Interactions

“…The authors were thus able to determine that the pPII region is the most favorable. In a more recent approach by Lanza et al [ 155 ] N-terminal blocked alanine peptides Ac-Ala-NH 2 (N = 2–4) were studied using MP2, CCSD(T) and DFT ab initio methods with implicit hydration. These authors found that nearly all major conformations (alpha helical, pPII, β-strand, and turn-like conformations) as well as a large number of mixed structures are energetically accessible, more in agreement with statistical coil models.…”