Statistical Analysis of the Role of Cavity Flexibility in Thermostability of Proteins
Conventional statistical investigations have primarily focused on the comparison of the simple one-dimensional characteristics of protein cavities, such as number, surface area, and volume. These studies have failed to discern the crucial distinctions in cavity properties between thermophilic and me...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | Polymers |
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| Online Access: | https://www.mdpi.com/2073-4360/16/2/291 |
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| author | So Yeon Hong Jihyun Yoon Young Joo An Siseon Lee Haeng-Geun Cha Ashutosh Pandey Young Je Yoo Jeong Chan Joo |
| author_facet | So Yeon Hong Jihyun Yoon Young Joo An Siseon Lee Haeng-Geun Cha Ashutosh Pandey Young Je Yoo Jeong Chan Joo |
| author_sort | So Yeon Hong |
| collection | DOAJ |
| description | Conventional statistical investigations have primarily focused on the comparison of the simple one-dimensional characteristics of protein cavities, such as number, surface area, and volume. These studies have failed to discern the crucial distinctions in cavity properties between thermophilic and mesophilic proteins that contribute to protein thermostability. In this study, the significance of cavity properties, i.e., flexibility and location, in protein thermostability was investigated by comparing structural differences between homologous thermophilic and mesophilic proteins. Three dimensions of protein structure were categorized into three regions (core, boundary, and surface) and a comparative analysis of cavity properties using this structural index was conducted. The statistical analysis revealed that cavity flexibility is closely related to protein thermostability. The core cavities of thermophilic proteins were less flexible than those of mesophilic proteins (averaged B’ factor values, −0.6484 and −0.5111), which might be less deleterious to protein thermostability. Thermophilic proteins exhibited fewer cavities in the boundary and surface regions. Notably, cavities in mesophilic proteins, across all regions, exhibited greater flexibility than those in thermophilic proteins (>95% probability). The increased flexibility of cavities in the boundary and surface regions of mesophilic proteins, as opposed to thermophilic proteins, may compromise stability. Recent protein engineering investigations involving mesophilic xylanase and protease showed results consistent with the findings of this study, suggesting that the manipulation of flexible cavities in the surface region can enhance thermostability. Consequently, our findings suggest that a rational or computational approach to the design of flexible cavities in surface or boundary regions could serve as an effective strategy to enhance the thermostability of mesophilic proteins. |
| first_indexed | 2024-03-08T10:36:17Z |
| format | Article |
| id | doaj.art-4411478137d34e86b3b3519811c5c361 |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-08T10:36:17Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-4411478137d34e86b3b3519811c5c3612024-01-26T18:14:21ZengMDPI AGPolymers2073-43602024-01-0116229110.3390/polym16020291Statistical Analysis of the Role of Cavity Flexibility in Thermostability of ProteinsSo Yeon Hong0Jihyun Yoon1Young Joo An2Siseon Lee3Haeng-Geun Cha4Ashutosh Pandey5Young Je Yoo6Jeong Chan Joo7Department of Chemical and Biological Engineering, Inha Technical College, Inha-ro 100, Michuhol-gu, Incheon 22212, Republic of KoreaDepartment of Biotechnology, The Catholic University of Korea, Bucheon-si 14662, Republic of KoreaDepartment of Biotechnology, The Catholic University of Korea, Bucheon-si 14662, Republic of KoreaDepartment of Biotechnology, The Catholic University of Korea, Bucheon-si 14662, Republic of KoreaDepartment of Biotechnology, The Catholic University of Korea, Bucheon-si 14662, Republic of KoreaInstitute for Water and Wastewater Technology, Durban University of Technology, 19 Steve Biko Road, Durban 4000, South AfricaSchool of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of KoreaDepartment of Biotechnology, The Catholic University of Korea, Bucheon-si 14662, Republic of KoreaConventional statistical investigations have primarily focused on the comparison of the simple one-dimensional characteristics of protein cavities, such as number, surface area, and volume. These studies have failed to discern the crucial distinctions in cavity properties between thermophilic and mesophilic proteins that contribute to protein thermostability. In this study, the significance of cavity properties, i.e., flexibility and location, in protein thermostability was investigated by comparing structural differences between homologous thermophilic and mesophilic proteins. Three dimensions of protein structure were categorized into three regions (core, boundary, and surface) and a comparative analysis of cavity properties using this structural index was conducted. The statistical analysis revealed that cavity flexibility is closely related to protein thermostability. The core cavities of thermophilic proteins were less flexible than those of mesophilic proteins (averaged B’ factor values, −0.6484 and −0.5111), which might be less deleterious to protein thermostability. Thermophilic proteins exhibited fewer cavities in the boundary and surface regions. Notably, cavities in mesophilic proteins, across all regions, exhibited greater flexibility than those in thermophilic proteins (>95% probability). The increased flexibility of cavities in the boundary and surface regions of mesophilic proteins, as opposed to thermophilic proteins, may compromise stability. Recent protein engineering investigations involving mesophilic xylanase and protease showed results consistent with the findings of this study, suggesting that the manipulation of flexible cavities in the surface region can enhance thermostability. Consequently, our findings suggest that a rational or computational approach to the design of flexible cavities in surface or boundary regions could serve as an effective strategy to enhance the thermostability of mesophilic proteins.https://www.mdpi.com/2073-4360/16/2/291protein thermostabilitycavityflexibilitythermophilic proteinsmesophilic proteinsstatistical analysis |
| spellingShingle | So Yeon Hong Jihyun Yoon Young Joo An Siseon Lee Haeng-Geun Cha Ashutosh Pandey Young Je Yoo Jeong Chan Joo Statistical Analysis of the Role of Cavity Flexibility in Thermostability of Proteins Polymers protein thermostability cavity flexibility thermophilic proteins mesophilic proteins statistical analysis |
| title | Statistical Analysis of the Role of Cavity Flexibility in Thermostability of Proteins |
| title_full | Statistical Analysis of the Role of Cavity Flexibility in Thermostability of Proteins |
| title_fullStr | Statistical Analysis of the Role of Cavity Flexibility in Thermostability of Proteins |
| title_full_unstemmed | Statistical Analysis of the Role of Cavity Flexibility in Thermostability of Proteins |
| title_short | Statistical Analysis of the Role of Cavity Flexibility in Thermostability of Proteins |
| title_sort | statistical analysis of the role of cavity flexibility in thermostability of proteins |
| topic | protein thermostability cavity flexibility thermophilic proteins mesophilic proteins statistical analysis |
| url | https://www.mdpi.com/2073-4360/16/2/291 |
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