Abstract
The dilemma of reconciling the contradictory evidence regarding the conformation of long solvated peptide chains is the so-called “reconciliation problem”. Clues regarding the stability of certain conformations likely lie in the electronic structure at the peptide–solvent interface, but the peptide–solvent interaction is not fully understood. Here, we study the influence of aqueous solvent on peptide conformations by using classical molecular dynamics (MD) and quantum mechanical/molecular mechanical (QM/MM) energy calculations. The model systems include an 11-residue peptide, XAO (XAO), where X, A, and O denote diaminobutyric acid, alanine, and ornithine, respectively, and a 9-mer (Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys). Spectroscopic and MD data present conflicting evidence regarding the structure of XAO in water; some results indicate that XAO adopts a polyproline II (P) conformation, whereas other findings suggest that XAO explores a range of conformations. To investigate this contradiction, we present here the results of MD simulations of XAO and the 9-mer in aqueous solution, combined with QM/MM energy calculations.
Highlights
The small, water-soluble XAO peptide, X2 A7 O2 (XAO), where X, A, and O denote diaminobutyric acid, alanine, and ornithine, respectively, has been the subject of several experimental and theoretical studies that deliver contradictory results regarding the amount of local structure in the unfolded state of peptides
The Φ-Ψ angle space sampled by XAO and the 9-mer was divided into six basins that span the Ramachandran plot (see Table 1 and Figure 2 for representative conformers of C7eq, αL, αR, 310, β, and polyproline II (PII))
The aim of our present investigation was to analyze the propensity of small peptides to exist in a PII conformation in aqueous solution
Summary
The small, water-soluble XAO peptide, X2 A7 O2 (XAO), where X, A, and O denote diaminobutyric acid, alanine, and ornithine, respectively, has been the subject of several experimental and theoretical studies that deliver contradictory results regarding the amount of local structure in the unfolded state of peptides. More recent NMR, CD, calorimetry, and small angle X-ray scattering (SAXS) measurements of solvated XAO indicate that the PII conformation is only one of several structures present in the conformational ensemble that includes α-helical and β-strand character [2,6,7,8]. These experimental data provoke the questions: what is the amount of Molecules 2018, 23, 2355; doi:10.3390/molecules23092355 www.mdpi.com/journal/molecules
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