2016 · Zhao — Dock 'n roll: folding of a silk-inspired polypeptide into an amyloid-like beta solenoid
Super-Abstract
This computational chemistry and molecular dynamics study analyses how a silk-inspired polypeptide folds into a stable beta-solenoid structure — a question in structural biology and materials science. The „hydrogen” in this paper refers exclusively to hydrogen bonds within protein structures, not to molecular hydrogen (H₂) as a therapeutic or biological gas. This paper has no relevance to H₂ supplementation or health. (Soft Matter, 2016.)
Commentary
This paper uses molecular dynamics simulations and ground-state energy analysis to determine the most stable folding configuration of silk-derived polypeptides with the repeating motif (GAGAGAGQ)₁₀. The central finding is that a „hydrophobic core” beta-solenoid structure — where hydrophobic side chains are buried inside — is energetically more stable than a „hydrophobic shell” configuration. The stability differences are explained in terms of intramolecular hydrogen bonds (i.e., N–H···O=C bonds within the peptide backbone), intermolecular hydrogen bonds in stacked structures, and hydrogen bonds between the peptide and surrounding water. The word „hydrogen” throughout this paper refers to hydrogen atoms in molecular bonds — specifically backbone amide hydrogens involved in beta-sheet hydrogen bonding — and is entirely unrelated to molecular hydrogen gas (H₂). This study is relevant to materials science, bionanotechnology, and amyloid fibril research, but has no bearing on H₂ biology.
Key quotes
- „A stack of two hydrophobic core molecules is energetically more favorable than a stack of two hydrophobic shell molecules.“ — the main structural conclusion: hydrophobic core configuration is more stable
- „The hydrophobic shell structure has type II' β turns whereas the core configuration has type II β turns; only the latter secondary structure agrees well with solid-state NMR experiments on a similar sequence.“ — NMR validation supports the hydrophobic core model
- „The core stack has a higher number of intra-molecular hydrogen bonds and a higher number of hydrogen bonds between stack and water than the shell stack.“ — the energetic advantage explained by hydrogen bonding patterns — referring to intramolecular bonds, not H₂ gas
Our assessment
This paper is a structural/computational chemistry study in materials science and soft matter physics. It has no connection to molecular hydrogen (H₂) as a biological or therapeutic agent. The „hydrogen” in this paper refers to hydrogen atoms forming intramolecular bonds within polypeptide structures. This paper provides no evidence relevant to H₂ health research. It appears in this database because of a keyword match on „hydrogen” in the literature search — it is not relevant to hydrogen therapy.
Study design
- Type: computational molecular dynamics simulation + ground-state energy analysis · Model: silk-inspired polypeptide (GAGAGAGQ)₁₀ — single molecules and two-molecule stacks · H₂ context: none — „hydrogen” = hydrogen atoms in peptide backbone bonds only
- Result: hydrophobic core beta-solenoid configuration is energetically more stable than hydrophobic shell; type II β turns (core) vs. type II' (shell); NMR-consistent; stacking increases intramolecular hydrogen bonds
Abstract
Polypeptides containing the motif ((GA)mGX)n occur in silk and have a strong tendency to self-assemble. For example, polypeptides containing (GAGAGAGX)n, where X = G or H have been observed to form filaments; similar sequences but with X = Q have been used in the design of coat proteins (capsids) for artificial viruses. The structure of the (GAGAGAGX)m filaments has been proposed to be a stack of peptides in a β roll structure with the hydrophobic side chains pointing outwards (hydrophobic shell). Another possible configuration, a β roll or β solenoid structure which has its hydrophobic side chains buried inside (hydrophobic core) was, however, overlooked. We perform ground state analysis as well as atomic-level molecular dynamics simulations, both on single molecules and on two-molecule stacks of the silk-inspired sequence (GAGAGAGQ)10, to decide whether the hydrophobic core or the hydrophobic shell configuration is the most stable one. We find that a stack of two hydrophobic core molecules is energetically more favorable than a stack of two hydrophobic shell molecules. A shell molecule initially placed in a perfect β roll structure tends to rotate its strands, breaking in-plane hydrogen bonds and forming out-of-plane hydrogen bonds, while a core molecule stays in the β roll structure. The hydrophobic shell structure has type II' β turns whereas the core configuration has type II β turns; only the latter secondary structure agrees well with solid-state NMR experiments on a similar sequence (GA)15. We also observe that the core stack has a higher number of intra-molecular hydrogen bonds and a higher number of hydrogen bonds between stack and water than the shell stack. Hence, we conclude that the hydrophobic core configuration is the most likely structure. In the stacked state, each peptide has more intra-molecular hydrogen bonds than a single folded molecule, which suggests that stacking provides the extra stability needed for molecules to reach the folded state.
Source & links
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