The elixir phase of chain molecules

Škrbić, Tatjana; Hoang, Trinh Xuan; Maritan, Amos; Banavar, Jayanth R.; Giacometti, Andrea

doi:10.1002/prot.25619

Cited by 17 publications

(15 citation statements)

References 50 publications

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“…To assure a wider variety of α-helix and β-sheet contents, we construct additional decoy structures in the following manner. Starting from the homo-polymer chain obtained using a coarse-grained model, 40 which possesses the relative contents of α-helix and β-sheet characteristic of each of the categories discussed below, we first try to achieve a maximally compact configuration both by increasing the range of attraction and by minimizing the gyration radius R g with a suitably devised annealing scheme. We then re-insert the atomistic content of the backbone and side chains using the Phyre2 backbone reconstruction tool 41 and the Scwrl4 side-chain reconstruction tool.…”

Section: E Preparation Of the Native And Decoy Structuresmentioning

confidence: 99%

Unraveling protein folding mechanism by analyzing the hierarchy of models with increasing level of detail

Hayashi

Yasuda

Škrbić

et al. 2017

The Journal of Chemical Physics

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Taking protein G with 56 residues for a case study, we investigate the mechanism of protein folding. In addition to its native structure possessing α-helix and β-sheet contents of 27% and 39%, respectively, we construct a number of misfolded decoys with a wide variety of α-helix and β-sheet contents. We then consider a hierarchy of 8 different models with increasing level of detail in terms of the number of entropic and energetic physical factors incorporated. The polyatomic structure is always taken into account, but the side chains are removed in half of the models. The solvent is formed by either neutral hard spheres or water molecules. Protein intramolecular hydrogen bonds (H-bonds) and protein-solvent H-bonds (the latter is present only in water) are accounted for or not, depending on the model considered. We then apply a physics-based free-energy function (FEF) corresponding to each model and investigate which structures are most stabilized. This special approach taken on a step-by-step basis enables us to clarify the role of each physical factor in contributing to the structural stability and separately elucidate its effect. Depending on the model employed, significantly different structures such as very compact configurations with no secondary structures and configurations of associated α-helices are optimally stabilized. The native structure can be identified as that with lowest FEF only when the most detailed model is employed. This result is significant for at least the two reasons: The most detailed model considered here is able to capture the fundamental aspects of protein folding notwithstanding its simplicity; and it is shown that the native structure is stabilized by a complex interplay of minimal multiple factors that must be all included in the description. In the absence of even a single of these factors, the protein is likely to be driven towards a different, more stable state.

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Section: E Preparation Of the Native And Decoy Structuresmentioning

confidence: 99%

Unraveling protein folding mechanism by analyzing the hierarchy of models with increasing level of detail

Hayashi

Yasuda

Škrbić

et al. 2017

The Journal of Chemical Physics

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“…A recent paper from polymer physics reports the discovery of a novel phase of matter, with multiple ground states made up of helices and almost planar sheets, similar to those in protein structures . Remarkably, this finding emerges spontaneously in linear polymer chains of identical backbone and side chain spheres subjected to a small number of geometrical constraints, without any necessity for hydrogen bonding, hydrophobic interactions, and the like.…”

Section: Discussionmentioning

confidence: 97%

Ramachandran maps for side chains in globular proteins

Rose

2019

Proteins

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The Ramachandran plot for backbone ϕ,ψ‐angles in a blocked monopeptide has played a central role in understanding protein structure. Curiously, a similar analysis for side chain χ‐angles has been comparatively neglected. Instead, efforts have focused on compiling various types of side chain libraries extracted from proteins of known structure. Departing from this trend, the following analysis presents backbone‐based maps of side chains in blocked monopeptides. As in the original ϕ,ψ‐plot, these maps are derived solely from hard‐sphere steric repulsion. Remarkably, the side chain biases exhibit marked similarities to corresponding biases seen in high‐resolution protein structures. Consequently, some of the entropic cost for side chain localization in proteins is prepaid prior to the onset of folding events because conformational bias is built into the chain at the covalent level. Furthermore, side chain conformations are seen to experience fewer steric restrictions for backbone conformations in either the α or β basins, those map regions where repetitive ϕ,ψ‐angles result in α‐helices or strands of β‐sheet, respectively. Here, these α and β basins are entropically favored for steric reasons alone; a blocked monopeptide is too short to accommodate the peptide hydrogen bonds that stabilize repetitive secondary structure. Thus, despite differing energetics, α/β‐basins are favored for both monopeptides and repetitive secondary structure, underpinning an energetically unfrustrated compatibility between these two levels of protein structure.

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“…First, adjacent spheres overlap [3, 4, 5] - σ is allowed to be larger than 1. Second, side spheres [6, 7, 8, 9, 10, 11, 12] of diameter σ s are attached (tangent to the main chain sphere in the negative normal direction in the local Frenet frame) to each of the main chain spheres except the first and the last. Other than the adjoining main chain spheres along the chain, none of the main chain and side spheres is allowed to overlap.…”

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confidence: 99%

Spontaneous dimensional reduction and novel ground state degeneracy in a simple chain model

Škrbić

Hoang

Giacometti

et al. 2021

Preprint

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Chain molecules play a key role in the polymer field and in living cells.Our focus is on a new homopolymer model of a linear chain molecule subject to an attractive self-interaction promoting compactness. We analyze the model using simple analytic arguments complemented by extensive computer simulations. We find several striking results: there is a first order transition from a high temperature random coil phase to a highly unusual low temperature phase; the modular ground states exhibit significant degeneracy; the ground state structures exhibit spontaneous dimensional reduction and have a two-layer structure; and the ground states are assembled from secondary motifs of helices and strands connected by tight loops. We discuss the similarities and notable differences between the ground state structures (we call these PoSSuM - Planar Structures with Secondary Motifs) in the novel phase and protein native state structures.

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The elixir phase of chain molecules

Cited by 17 publications

References 50 publications

Unraveling protein folding mechanism by analyzing the hierarchy of models with increasing level of detail

Unraveling protein folding mechanism by analyzing the hierarchy of models with increasing level of detail

Ramachandran maps for side chains in globular proteins

Spontaneous dimensional reduction and novel ground state degeneracy in a simple chain model

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