Prediction of the Assembly Process and Structure of Heteromultimeric Proteins via Multilevel Conformational Merging

doi:10.1007/s40242-025-5157-y

Chemical Research in Chinese Universities ›› 2025, Vol. 41 ›› Issue (5): 1144-1156.doi: 10.1007/s40242-025-5157-y

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Prediction of the Assembly Process and Structure of Heteromultimeric Proteins via Multilevel Conformational Merging

ZHANG Dinglin^1,2, LI Yan^1,2, LIU Ye^1,2, LI Guohui^1,2, CHU Huiying^1,2

1. Interdisciplinary Research Center for Biology and Chemistry, Liaoning Normal University, Dalian 116029, P. R. China;
2. Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, P. R. China

Received:2025-07-25 Accepted:2025-09-08 Online:2025-10-01 Published:2025-09-26
Contact: CHU Huiying, E-mail: chuhy2009@dicp.ac.cn;LI Guohui, E-mail: ghli@dicp.ac.cn;ZHANG Dinglin, E-mail: dlzhang@dicp.ac.cn E-mail:chuhy2009@dicp.ac.cn;ghli@dicp.ac.cn;dlzhang@dicp.ac.cn
Supported by:
This work was supported by the National Key R&D Program of China (No. 2023YFF1204903) and the Liaoning Revitalization Talents Program, China (No. XLYC2402023).

Abstract

Abstract: Understanding the assembly pathways of heteromultimeric protein complexes is crucial for deciphering their functional mechanisms. However, traditional computational methods often struggle with the combinatorial NP-hard (non-deterministic polynomial-time hard) problem. This study employs a computational method, multilevel merge dock (MuMD), which uses a competition-based strategy to simulate the actual assembly process of heteromultimeric proteins. By avoiding the combinatorial NP-hard problem typically associated with the exhaustive conformation sampling, MuMD reduces the need to generate and evaluate a large number of conformations, thereby reducing computational costs while improving accuracy and efficiency. In the process, the ZDOCK scoring function is used to select optimal protein pair, followed by subsequent assembly using the roulette-wheel algorithm. Each component undergoes competition during the assembly process, with the subcomplex having the highest score taking priority in assembly steps. The results showed that MuMD can effectively simulate the dynamic assembly process of heteromultimeric protein complexes. Additionally, it accurately predicts the assembly pathway of the heteromultimeric protein complexes. Notably, MuMD method demonstrates significant advantages in accurately predicting the assembly pathways of complexes with fewer than 6 chains. This work provides an efficient and accurate tool for studying protein complex assembly.

Key words: Heteromultimeric protein complex, Protein docking, Assembly order, Assembly structure

ZHANG Dinglin, LI Yan, LIU Ye, LI Guohui, CHU Huiying. Prediction of the Assembly Process and Structure of Heteromultimeric Proteins via Multilevel Conformational Merging[J]. Chemical Research in Chinese Universities, 2025, 41(5): 1144-1156.

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Prediction of the Assembly Process and Structure of Heteromultimeric Proteins via Multilevel Conformational Merging

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