Aug 2026· Biomacromolecules· 0 citations· 51 references
Abstract
The structural feasibility of chain folding within an accepted cellulose-II structure is investigated in this study. We incorporate 3-residue and 5-residue folded glucosyl turns into a cellulose-II fibril crystal model to assess if the dominant structure can be retained. Ten candidate turn models were generated by metadynamics simulations and ranked by semiempirical quantum mechanical energies. Across >30 independent 300 ns molecular dynamics trajectories, the crystalline core retains its unit cell parameters, X-ray diffraction pattern, hydrogen bonding network, and canonical 4C1 ring conformation. This suggests that, should such folds be present, they need not compromise bulk crystalline integrity. No significant fibril twisting was observed in either the unfolded or chain-fold models. At the chain-folding ends of the fibril, high-energy boat and skew-boat conformations drive hydroxymethyl rotamer redistribution and noncanonical hydrogen bonding contacts. The greater structural flexibility of the 5-residue folded turns allows the chain-fold ends to access a broader conformational space, yet the structural perturbation remains localized within the same 3-residue region as the 3-residue folded turns. The 3-residue turn is therefore considered the more plausible chain-fold structure for cellulose-II, should such a structure actually exist in reality.
This work presents a minimal coarse-grained molecular dynamics model for the coil-helix transition in polymers. We demonstrate that the addition of a Morse potential to a freely jointed chain with volume and bond potentials is sufficient to reproduce the essential thermodynamic features of the transition. From the simulations performed, the Zimm-Bragg propagation parameter s and nucleation parameter σ are extracted, providing quantitative measures of helical propensity and cooperativity, respectively. To illustrate the versatility of the model, this study systematically varies the spacing between hydrogen-bonding monomers using an i → i + m motif, with m = 4, 5, and 6 corresponding to coarse-grained representations of α-, π-, and 1-7 helices. This approach is used to evaluate how hydrogen-bond spacing influences the transition behavior and the resulting cooperativity. As the monomer spacing m between hydrogen-bonding pairs increases, the number of monomers that must be confined for the first hydrogen bond to form also increases, leading to increased cooperativity (lower nucleation parameter σ) and a sharper transition, as reflected in the simulation results. This behavior is consistent with that observed in natural helices of different types, underscoring the model's ability to capture how molecular architecture governs helix formation.
Karthik C Sinha, Alexey A. Gavrilov, A. Rumyantsev· Journal of Chemical Physics· 1 citation
Macromolecular coil-to-helix transitions simultaneously modify local geometry and persistence length, driving complex changes in overall chain size. Here, we apply the wormlike (persistent) chain model to both coil and helical fragments to examine how the degree of helicity, θ, and average helical fragment length, kh, dictate global chain dimensions. Using scaling arguments, we construct a conformational diagram comprising six distinct regimes for the end-to-end distance. We then employ a minimal coarse-grained molecular dynamics model to verify the theory. Mapping structural properties extracted from these simulations onto the proposed regime diagram enables direct quantitative comparison. This, alongside microscopic conformational analysis, corroborates our theoretical framework. We highlight that the competition between local chain compactization and increased stiffness upon helix formation produces a non-monotonic behavior of the end-to-end distance. Furthermore, to demonstrate the generality of our approach, we systematically vary the hydrogen-bonding monomer spacing m for pairs {i, i + m}. Spacings of m = 4, 5, and 6 are used as coarse-grained representations of α-, π-, and 1-7 helices, respectively. As m increases, the helix becomes locally more compact while its persistence length grows. The regime diagrams constructed for these distinct configurations, combined with robust quantitative agreement between theory and simulation, demonstrate that our framework effectively captures how variations in helix geometry and stiffness control macromolecular dimensions across the transition.
Karthik C Sinha, Alexey A. Gavrilov, A. Rumyantsev· Journal of Chemical Physics· 1 citation
Together, these results show that designed repeat-protein folding is governed by seed formation, interface propagation, and terminal boundary conditions, and establish intramolecular crosslinking as a strategy for rationally reshaping folding landscapes in designed proteins.
Melanie Weiß, Anna Lisa Heit, L. Milles et al.· bioRxiv· 0 citations
We use atomistic molecular dynamics simulations to determine the equilibrium fraction of short-chain branches grafted to periodic polyethylene chains on the surface of a crystalline slab that are included within the crystalline region that grows onto the crystalline slab after a temperature quench. From this and the Boltzmann principle, we estimate the corresponding crystal-inclusion free energy as a function of temperature and of branch length ranging from methyl to hexyl groups. Snapshots show that, if included into the crystal, side groups larger than methyl need to be accommodated by defects including crystal distortion, chain folding, or chain ends, where the latter indicates a dependence on molecular weight of the crystal-inclusion energy. The different mechanisms of short-chain accommodation may be responsible for our observations of the effect of branch length and temperature on the crystal-inclusion energy. At 360 K, the crystal-inclusion energy increases from methyl to ethyl branches but remains almost unchanged at around 25 kJ/mol for larger side groups. For a methyl branch, the crystal-inclusion energy increases as quench temperature decreases from 360 to 300 K while the larger branches (ethyl and hexyl groups) show the opposite trend.
Yanan Gong, Ronald G. Larson· Chinese Physics B· 0 citations
Amylose contributes to starch crystallinity, but the stability of packed amylose double helices in water at elevated temperature remains insufficiently characterized. Here, we used molecular dynamics simulations to test whether chain length affects the short-timescale stability of A-type amylose oligomers in water. Six systems differing in chain length (6, 12, or 24 glucose units per chain) and oligomer size (isolated double strand or dodecamer of six double strands) were simulated, and five independent 1-μs production runs were analyzed for each simulated condition. Oligomers with six glucose units showed structural collapse accompanied by increased water penetration. By contrast, dodecamers with 12 or 24 glucose units largely retained packed double-helical organization over the simulated timescale, although fraying was observed at their ends. These results indicate that chain length and lateral packing strongly affect the early structural response of amylose-like crystalline segments in hot water. The present simulations do not establish the ultimate fate of longer oligomers at longer timescales, but they identify a relative stability difference that is relevant to molecular interpretations of hydration-driven disordering in starch.
M. Araki, Biao Ma, Yukari Sagae et al.· bioRxiv· 0 citations
The thermal stability of collagen triple helices is strongly influenced by the amino acid sequence of the repeating Gly–X–Y tripeptides, yet how these residue-specific interactions are integrated within an extended triple helix to determine thermal behavior remains poorly understood. Here, we addressed this question using recombinant collagen mimetic peptides (rCMPs) containing extended native sequences from the α1(I) and α2(I) chains of human type I collagen. Triple-helix formation was nucleated by a C-terminal foldon domain and further stabilized by interchain disulfide crosslinking, allowing the apparent melting temperature (Tₘ) to reflect interactions within the triple-helical domain independent of nucleation. The stabilizing effects of Pro and Y-position Arg identified in host-guest peptides were largely preserved in extended triple helices, whereas the proposed Lys–Gly–Glu (KGE) interchain salt bridge produced little measurable stabilization, demonstrating the influence of sequence context. Remarkably, identical triple-helical sequences exhibited markedly different thermal behavior when unfolding was initiated under different conditions. Nevertheless, extended triple helices differing substantially in sequence and length retained an apparently two-state thermal transition. These findings support a mechanism in which unfolding is preferentially initiated within regions of lower intrinsic stability, while the continuity of the triple helix couples neighboring regions into a cooperative unfolding process throughout the helix. This mechanism provides a plausible explanation for the longstanding paradox that extended collagen triple helices exhibit persistent sequence-dependent thermodynamic heterogeneity despite a two-state thermal transition, and a framework for investigating how sequence-dependent stability contributes to the structure and function of collagen molecules. TOC
Sophie Youngji Xu, Sam Wong, Sally Tan et al.· bioRxiv· 0 citations
