Coarse-Grained Modeling of Multiple Pathways in Conformational Transitions of Multi-Domain Proteins
| Autor: | Chigusa Kobayashi, Ai Shinobu, Yasuhiro Matsunaga, Yuji Sugita |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Physics
010304 chemical physics Protein Conformation General Chemical Engineering Adenylate Kinase Proteins General Chemistry Molecular Dynamics Simulation Library and Information Sciences 01 natural sciences 0104 chemical sciences Computer Science Applications ADK 010404 medicinal & biomolecular chemistry Multi domain Molecular dynamics Protein structure 0103 physical sciences Bennett acceptance ratio Biological system Coarse-grained modeling Mixing (physics) |
| Zdroj: | Journal of Chemical Information and Modeling. 61:2427-2443 |
| ISSN: | 1549-960X 1549-9596 |
| Popis: | Large-scale conformational transitions in multi-domain proteins are often essential for their functions. To investigate the transitions, it is necessary to explore multiple potential pathways, which involve different intermediate structures. Here, we present a multi-basin (MB) coarse-grained (CG) structure-based Go̅ model for describing transitions in proteins with more than two moving domains. This model is an extension of our dual-basin Go̅ model in which system-dependent parameters are determined systematically using the multistate Bennett acceptance ratio method. In the MB Go̅ model for multi-domain proteins, we assume that intermediate structures may have partial inter-domain native contacts. This approach allows us to search multiple transition pathways that involve distinct intermediate structures using the CG molecular dynamics (MD) simulations. We apply this scheme to an enzyme, adenylate kinase (AdK), which has three major domains and can move along two different pathways. Using the optimized mixing parameters for each pathway, AdK shows frequent transitions between the Open, Closed, and the intermediate basins and samples a wide variety of conformations within each basin. The explored multiple transition pathways could be compared with experimental data and examined in more detail by atomistic MD simulations. |
| Databáze: | OpenAIRE |
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