New Insight into Mechanisms of Protein Adaptation to High Temperatures: A Comparative Molecular Dynamics Simulation Study of Thermophilic and Mesophilic Subtilisin-Like Serine Proteases
In high-temperature environments, thermophilic proteins must possess enhanced thermal stability in order to maintain their normal biological functions. However, the physicochemical basis of the structural stability of thermophilic proteins at high temperatures remains elusive. In this study, we perf...
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/9/3128 |
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| author | Peng Sang Shu-Qun Liu Li-Quan Yang |
| author_facet | Peng Sang Shu-Qun Liu Li-Quan Yang |
| author_sort | Peng Sang |
| collection | DOAJ |
| description | In high-temperature environments, thermophilic proteins must possess enhanced thermal stability in order to maintain their normal biological functions. However, the physicochemical basis of the structural stability of thermophilic proteins at high temperatures remains elusive. In this study, we performed comparative molecular dynamics simulations on thermophilic serine protease (THM) and its homologous mesophilic counterpart (PRK). The comparative analyses of dynamic structural and geometrical properties suggested that THM adopted a more compact conformation and exhibited more intramolecular interactions and lower global flexibility than PRK, which could be in favor of its thermal stability in high-temperature environments. Comparison between protein solvent interactions and the hydrophobicity of these two forms of serine proteases showed that THM had more burial of nonpolar areas, and less protein solvent hydrogen bonds (HBs), indicating that solvent entropy maximization and mobility may play a significant role in THM’s adaption to high temperature environments. The constructed funnel-like free energy landscape (FEL) revealed that, in comparison to PRK, THM had a relatively flat and narrow free energy surface, and a lower minimum free energy level, suggesting that the thermophilic form had lower conformational diversity and flexibility. Combining the FEL theory and our simulation results, we conclude that the solvent (entropy force) plays a significant role in protein adaption at high temperatures. |
| first_indexed | 2024-03-10T20:10:28Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:10:28Z |
| publishDate | 2020-04-01 |
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| spelling | doaj.art-65951d954e804a368607d007d06230ba2023-11-19T22:59:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01219312810.3390/ijms21093128New Insight into Mechanisms of Protein Adaptation to High Temperatures: A Comparative Molecular Dynamics Simulation Study of Thermophilic and Mesophilic Subtilisin-Like Serine ProteasesPeng Sang0Shu-Qun Liu1Li-Quan Yang2College of Agriculture and Biological Science, Dali University, Dali 671000, ChinaState Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming 650000, ChinaCollege of Agriculture and Biological Science, Dali University, Dali 671000, ChinaIn high-temperature environments, thermophilic proteins must possess enhanced thermal stability in order to maintain their normal biological functions. However, the physicochemical basis of the structural stability of thermophilic proteins at high temperatures remains elusive. In this study, we performed comparative molecular dynamics simulations on thermophilic serine protease (THM) and its homologous mesophilic counterpart (PRK). The comparative analyses of dynamic structural and geometrical properties suggested that THM adopted a more compact conformation and exhibited more intramolecular interactions and lower global flexibility than PRK, which could be in favor of its thermal stability in high-temperature environments. Comparison between protein solvent interactions and the hydrophobicity of these two forms of serine proteases showed that THM had more burial of nonpolar areas, and less protein solvent hydrogen bonds (HBs), indicating that solvent entropy maximization and mobility may play a significant role in THM’s adaption to high temperature environments. The constructed funnel-like free energy landscape (FEL) revealed that, in comparison to PRK, THM had a relatively flat and narrow free energy surface, and a lower minimum free energy level, suggesting that the thermophilic form had lower conformational diversity and flexibility. Combining the FEL theory and our simulation results, we conclude that the solvent (entropy force) plays a significant role in protein adaption at high temperatures.https://www.mdpi.com/1422-0067/21/9/3128solventserine proteasesmolecular dynamics simulationfree energy landscape |
| spellingShingle | Peng Sang Shu-Qun Liu Li-Quan Yang New Insight into Mechanisms of Protein Adaptation to High Temperatures: A Comparative Molecular Dynamics Simulation Study of Thermophilic and Mesophilic Subtilisin-Like Serine Proteases International Journal of Molecular Sciences solvent serine proteases molecular dynamics simulation free energy landscape |
| title | New Insight into Mechanisms of Protein Adaptation to High Temperatures: A Comparative Molecular Dynamics Simulation Study of Thermophilic and Mesophilic Subtilisin-Like Serine Proteases |
| title_full | New Insight into Mechanisms of Protein Adaptation to High Temperatures: A Comparative Molecular Dynamics Simulation Study of Thermophilic and Mesophilic Subtilisin-Like Serine Proteases |
| title_fullStr | New Insight into Mechanisms of Protein Adaptation to High Temperatures: A Comparative Molecular Dynamics Simulation Study of Thermophilic and Mesophilic Subtilisin-Like Serine Proteases |
| title_full_unstemmed | New Insight into Mechanisms of Protein Adaptation to High Temperatures: A Comparative Molecular Dynamics Simulation Study of Thermophilic and Mesophilic Subtilisin-Like Serine Proteases |
| title_short | New Insight into Mechanisms of Protein Adaptation to High Temperatures: A Comparative Molecular Dynamics Simulation Study of Thermophilic and Mesophilic Subtilisin-Like Serine Proteases |
| title_sort | new insight into mechanisms of protein adaptation to high temperatures a comparative molecular dynamics simulation study of thermophilic and mesophilic subtilisin like serine proteases |
| topic | solvent serine proteases molecular dynamics simulation free energy landscape |
| url | https://www.mdpi.com/1422-0067/21/9/3128 |
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