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Exploring protein conformations by cluster-guided iterative multiple independent molecular dynamics simulations |
| Chengtao Ding(丁成涛)1,2,†, Guanglin Chen(陈光临)3,†, Qingguo Gong(龚庆国)2, and Zhiyong Zhang(张志勇)2,3,‡ |
1 Department of Clinical Laboratory Center, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China;
2 Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China;
3 Department of Physics and Anhui Center for Fundamental Science in Theoretical Physics, University of Science and Technology of China, Hefei 230026, China |
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Abstract Enhanced sampling methods in molecular dynamics (MD) simulations have been gaining popularity in the past decades because they can explore conformations of proteins more efficiently than conventional MD simulations. In this paper, we implement a protocol of enhanced sampling that combines iterative multiple independent MD simulations and cluster analysis. After a set of independent simulations, the combined trajectory is divided into clusters. The representative structures picked from the clusters are utilized to start the next cycle of MD simulations. By using different strategies to pick the representative structures, the enhanced sampling can be either targeted or non-targeted. Two multi-domain proteins, Escherichia coli adenylate kinase (AdK) and the three-domain (PHD-Bromo-PWWP) structure in the BS69 protein, were selected to test the method. The data indicate that conformations of the proteins can be efficiently explored, and the results show better agreement with the experimental data than those obtained through conventional MD simulations.
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Received: 28 July 2025
Revised: 11 September 2025
Accepted manuscript online: 18 September 2025
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PACS:
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87.15.ap
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(Molecular dynamics simulation)
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87.14.E-
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(Proteins)
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87.15.B-
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(Structure of biomolecules)
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| Fund: Research and Development Program of China (Grant No. 2021YFA1301504), Anhui University of Chinese Medicine 2024 Clinical Research Project (Grant No. 2024YFYLCZX26), the National Natural Science Foundation of China (Grant No. 91953101), and Chinese Academy of Sciences Strategic Priority Research Program (Grant No. XDB37040202). |
Corresponding Authors:
Zhiyong Zhang
E-mail: zzyzhang@ustc.edu.cn
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Cite this article:
Chengtao Ding(丁成涛), Guanglin Chen(陈光临), Qingguo Gong(龚庆国), and Zhiyong Zhang(张志勇) Exploring protein conformations by cluster-guided iterative multiple independent molecular dynamics simulations 2026 Chin. Phys. B 35 058702
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