Topological and sequence information predict that foldons organize a partially overlapped and hierarchical structure

Sugita, Masatake; Matsuoka, Masanari; Kikuchi, Takeshi

doi:10.1002/prot.24874

Cited by 4 publications

(7 citation statements)

References 80 publications

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“…In myoglobin, helices A, G, H and the C-terminal half of helix B have high early folding scores compared to the C, D, E and F helices. The predictions therefore agree well with the experimentally validated folding profile of myoglobin, which computational folding studies were unable to reproduce 28 : the high helical content of myoglobin, with its reliance on local contacts, make the study of transition states starting from the final structure very challenging. In leghemoglobin, helices G, H and to a lesser extent B give higher scores and indeed do fold early.…”

Section: Resultssupporting

confidence: 67%

Exploring the Sequence-based Prediction of Folding Initiation Sites in Proteins

Raimondi

Orlando

Pancsa

et al. 2017

Sci Rep

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Protein folding is a complex process that can lead to disease when it fails. Especially poorly understood are the very early stages of protein folding, which are likely defined by intrinsic local interactions between amino acids close to each other in the protein sequence. We here present EFoldMine, a method that predicts, from the primary amino acid sequence of a protein, which amino acids are likely involved in early folding events. The method is based on early folding data from hydrogen deuterium exchange (HDX) data from NMR pulsed labelling experiments, and uses backbone and sidechain dynamics as well as secondary structure propensities as features. The EFoldMine predictions give insights into the folding process, as illustrated by a qualitative comparison with independent experimental observations. Furthermore, on a quantitative proteome scale, the predicted early folding residues tend to become the residues that interact the most in the folded structure, and they are often residues that display evolutionary covariation. The connection of the EFoldMine predictions with both folding pathway data and the folded protein structure suggests that the initial statistical behavior of the protein chain with respect to local structure formation has a lasting effect on its subsequent states.

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Section: Resultssupporting

confidence: 67%

Exploring the Sequence-based Prediction of Folding Initiation Sites in Proteins

Raimondi

Orlando

Pancsa

et al. 2017

Sci Rep

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“…It is well-known that a Gō model technique can reproduce the various properties of folding mechanisms of proteins rather precisely such as the relationship between topology and folding rate of a protein, [ 16 – 18 ] the presence or absence of folding intermediates [ 19 – 21 ] and the folding pathways [ 19 , 22 , 23 ]. It has been also demonstrated that our Gō model reproduces the experimentally observed folding processes of SH3 domain, GB proteins and ferredoxin [ 13 – 15 ]. A molecular dynamics (MD) simulation is also widely used to analyze the folding of a protein, but it is applied for a protein with several ten residues.…”

Section: Introductionmentioning

confidence: 68%

“…A Gō model includes only inter-residue attractive interactions observed in the native structure of a protein and it has been confirmed that a Gō model reproduces the folding process of a protein precisely. In the present study, a coarse-grained Gō model that we developed in our previous articles was used [13,14] It has been confirmed that our method can reproduce the experimentally observed folding processes of SH3 domain, GB proteins and ferredoxin [13][14][15]. We briefly explain this method as follows.…”

Section: Gō Modelmentioning

confidence: 93%

“…When Θ ij exceeds a cutoff value, B ij~0 , the residues cannot make a contact. A cutoff value a Θ = 0.6π was used [15]. For the terminal residues, B ij = 1 because we cannot define the vector h i .…”

Section: Gō Modelmentioning

confidence: 99%

“…In the present study, we apply the coarse-grained Gō model which we have developed [ 13 – 15 ]. This technique incorporates the effects of side chains implicitly into a coarse-grained Gō model [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Analyses of the folding sites of irregular β-trefoil fold proteins through sequence-based techniques and Gō-model simulations

Kimura

Aumpuchin

Hamaue

et al. 2020

BMC Mol and Cell Biol

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Background: The details of the folding mechanisms have not yet been fully understood for many proteins, and it is believed that the information on the folding mechanism of a protein is encoded in its amino acid sequence. βtrefoil proteins are known to have the same 3D scaffold, namely, a threefold symmetric scaffold, despite the proteins' low sequence identity among superfamilies. In this study, we extract an initial folding unit from the amino acid sequences of irregular β-trefoil proteins by constructing an average distance map (ADM) and utilizing interresidue average distance statistics to determine the relative contact frequencies for residue pairs in terms of F values. We compare our sequence-based prediction results with the packing between hydrophobic residues in native 3D structures and a Gō-model simulation. Results: The ADM and F-value analyses predict that the N-terminal and C-terminal regions are compact and that the hydrophobic residues at the central region can be regarded as an interaction center with other residues. These results correspond well to those of the Gō-model simulations. Moreover, our results indicate that the irregular parts in the β-trefoil proteins do not hinder the protein formation. Conserved hydrophobic residues on the β5 strand are always the interaction center of packing between the conserved hydrophobic residues in both regular and irregular β-trefoil proteins. Conclusions: We revealed that the β5 strand plays an important role in β-trefoil protein structure construction. The sequence-based methods used in this study can extract the protein folding information from only amino acid sequence data, and well corresponded to 3D structure-based Gō-model simulation and available experimental results.

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Prediction of the initial folding sites and the entire folding processes for Ig‐like beta‐sandwich proteins

2019

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Describing the whole story of protein folding is currently the main enigmatic problem in molecular bioinformatics study. Protein folding mechanisms have been intensively investigated with experimental as well as simulation techniques. Since a protein folds into its specific 3D structure from a unique amino acid sequence, it is interesting to extract as much information as possible from the amino acid sequence of a protein. Analyses based on inter‐residue average distance statistics and a coarse‐grained Gō‐model simulation were conducted on Ig and FN3 domains of a titin protein to decode the folding mechanisms from their sequence data and native structure data, respectively. The central region of all domains was predicted to be an initial folding unit, that is, stable in an early state of folding. This common feature coincides well with the experimental results and underscores the significance of the β‐sandwich proteins' common structure, namely, the key strands for folding and the Greek‐key motif, which is located in the central region. We confirmed that our sequence‐based techniques were able to predict the initial folding event just next to the denatured state and that a 3D‐based Gō‐model simulation can be used to investigate the whole process of protein folding.

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Topological and sequence information predict that foldons organize a partially overlapped and hierarchical structure

Cited by 4 publications

References 80 publications

Exploring the Sequence-based Prediction of Folding Initiation Sites in Proteins

Exploring the Sequence-based Prediction of Folding Initiation Sites in Proteins

Analyses of the folding sites of irregular β-trefoil fold proteins through sequence-based techniques and Gō-model simulations

Prediction of the initial folding sites and the entire folding processes for Ig‐like beta‐sandwich proteins

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