Analyses of the folding sites of irregular β-trefoil fold proteins through sequence-based techniques and Gō-model simulations
Abstract 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. β-trefoil proteins are known to have the same 3D scaffold, namely, a th...
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doaj-1ef5f4aa13764c3ca3e7f072e7c1912d2020-11-25T03:00:41ZengBMCBMC Molecular and Cell Biology2661-88502020-04-0121111710.1186/s12860-020-00271-4Analyses of the folding sites of irregular β-trefoil fold proteins through sequence-based techniques and Gō-model simulationsRisako Kimura0Panyavut Aumpuchin1Shoya Hamaue2Takumi Shimomura3Takeshi Kikuchi4Department of Bioinformatics, College of Life Sciences, Ritsumeikan UniversityNational Center for Genetic Engineering and Biotechnology (BIOTEC)Department of Bioinformatics, College of Life Sciences, Ritsumeikan UniversityDepartment of Bioinformatics, College of Life Sciences, Ritsumeikan UniversityDepartment of Bioinformatics, College of Life Sciences, Ritsumeikan UniversityAbstract 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. β-trefoil proteins are known to have the same 3D scaffold, namely, a three-fold 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 inter-residue 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.http://link.springer.com/article/10.1186/s12860-020-00271-4β-Trefoil foldFolding mechanismInter-residue average distance statisticsConserved hydrophobic residuesGō-model simulation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Risako Kimura Panyavut Aumpuchin Shoya Hamaue Takumi Shimomura Takeshi Kikuchi |
spellingShingle |
Risako Kimura Panyavut Aumpuchin Shoya Hamaue Takumi Shimomura Takeshi Kikuchi Analyses of the folding sites of irregular β-trefoil fold proteins through sequence-based techniques and Gō-model simulations BMC Molecular and Cell Biology β-Trefoil fold Folding mechanism Inter-residue average distance statistics Conserved hydrophobic residues Gō-model simulation |
author_facet |
Risako Kimura Panyavut Aumpuchin Shoya Hamaue Takumi Shimomura Takeshi Kikuchi |
author_sort |
Risako Kimura |
title |
Analyses of the folding sites of irregular β-trefoil fold proteins through sequence-based techniques and Gō-model simulations |
title_short |
Analyses of the folding sites of irregular β-trefoil fold proteins through sequence-based techniques and Gō-model simulations |
title_full |
Analyses of the folding sites of irregular β-trefoil fold proteins through sequence-based techniques and Gō-model simulations |
title_fullStr |
Analyses of the folding sites of irregular β-trefoil fold proteins through sequence-based techniques and Gō-model simulations |
title_full_unstemmed |
Analyses of the folding sites of irregular β-trefoil fold proteins through sequence-based techniques and Gō-model simulations |
title_sort |
analyses of the folding sites of irregular β-trefoil fold proteins through sequence-based techniques and gō-model simulations |
publisher |
BMC |
series |
BMC Molecular and Cell Biology |
issn |
2661-8850 |
publishDate |
2020-04-01 |
description |
Abstract 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. β-trefoil proteins are known to have the same 3D scaffold, namely, a three-fold 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 inter-residue 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. |
topic |
β-Trefoil fold Folding mechanism Inter-residue average distance statistics Conserved hydrophobic residues Gō-model simulation |
url |
http://link.springer.com/article/10.1186/s12860-020-00271-4 |
work_keys_str_mv |
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