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Molecular dynamics simulation of the effect of temperature on the conformation of ubiquitin protein

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Abstract

Content

Ubiquitin, a ubiquitous small protein found in all living organisms, is crucial for tagging proteins earmarked for degradation and holds pivotal importance in biomedicine. Protein functionality is intricately linked to its structure. To comprehend the impact of diverse temperatures on ubiquitin protein structure, our study delved into the energy landscape, hydrogen bonding, and overall structural stability of ubiquitin protein at varying temperatures. Through meticulous analysis of root mean square deviation and root mean square fluctuation, we validated the robustness of the simulation conditions employed. Within our simulated system, the bonding energy and electrostatic potential energy exhibited linear augmentation, while the van der Waals energy demonstrated a linear decline. Additionally, our findings highlighted that the α-Helix secondary structure of the ubiquitin protein gradually transitions toward helix destabilization under high-temperature conditions. The secondary structure of ubiquitin protein experiences distinct changes under varying temperatures. The outcomes of our molecular simulations offer a theoretical framework that enhances our comprehension of how temperature impacts the structural stability of ubiquitin protein. These insights contribute not only to a deeper understanding of iniquity’s behavior but also hold broader implications in the realm of biomedicine and beyond.

Methods

All the MD simulations were performed using the GROMACS software with GROMOS96 force field and SPC for water. The ubiquitin protein was put in the center of a cubic box with a length of 8 nm, a setting that allowed > 0.8 nm in the minimal distance between the protein surface and the box wall. To remove the possible coordinate collision of the configurations, in the beginning, the steepest descent method was used until the maximum force between atoms was under 100 kJ/mol·nm with a 0.01 nm step size. Minimization was followed by 30 ps of position-restrained MD simulation. The protein was restrained to its initial position, and the solvent was freely equilibrated. The product phase was obtained with the whole system simulated for 10 ns without any restraint using an integral time step of 1 fs with different temperatures. The cutoff for short-range electronic interaction was set to 1.5 nm. The long-range interactions were treated with a particle-mesh Ewald (PME) method with a grid width of 1.2 nm.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This research was supported by the Joint Funds of Zhejiang Provincial Natural Science Foundation of China under Grant No. LZY24B030001, Lab Open Project (No. KFXM202204) funded by Zhaoyang Ju, and Zhaoyang Ju project of Student Innovation and Entrepreneurship Training Program (No. Q23X001), Yihang Yu project of the Research Fund for the Program of “Xinmiao” (Potential) Talents in Zhejiang Province (No. 2022R435A002). The work was carried out at the Shanxi Supercomputing Center of China, and the calculations were performed on TianHe-2.

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Authors and Affiliations

  1. College of Chemical & Material Engineering, Quzhou University, Quzhou, 324000, Zhejiang, China

    Junpeng Hu, Shanshan Song, Mengting Yu, Yihang Yu & Zhaoyang Ju

  2. Institute of Zhejiang University-Quzhou, Quzhou, 324003, Zhejiang, China

    Xiaoyong Cao

  3. Zhejiang Qingke Environmental Technology Co, Ltd, 324004, QuzhouZhejiang, China

    Yufen Wang

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  1. Junpeng Hu
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  2. Shanshan Song
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  3. Mengting Yu
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Contributions

Junpeng Hu: drafted the manuscript and performed the data analysis. Shanshan Song: collected the data. MengtingYu: reviewed the manuscript. Yihang Yu: verified the analytical methods. Zhaoyang Ju: reviewed the manuscript and designed the study. Yufen Wang: reviewed the manuscript. Xiaoyong Cao: reviewed the manuscript.

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Correspondence to Zhaoyang Ju or Xiaoyong Cao.

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Hu, J., Song, S., Yu, M. et al. Molecular dynamics simulation of the effect of temperature on the conformation of ubiquitin protein. J Mol Model 30, 134 (2024). https://doi.org/10.1007/s00894-024-05928-x

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