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通过混合分辨率 SAXS 约束分子动力学确定蛋白质结构组合。

Determination of Protein Structural Ensembles by Hybrid-Resolution SAXS Restrained Molecular Dynamics.

机构信息

Dipartimento di Bioscienze, Università degli Studi di Milano, via Celoria 26, 20133 Milano, Italy.

Department of Chemistry and Institute of Advanced Study, Technical University of Munich, Garching 85747, Germany.

出版信息

J Chem Theory Comput. 2020 Apr 14;16(4):2825-2834. doi: 10.1021/acs.jctc.9b01181. Epub 2020 Mar 11.

DOI:10.1021/acs.jctc.9b01181
PMID:32119546
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7997378/
Abstract

Small-angle X-ray scattering (SAXS) experiments provide low-resolution but valuable information about the dynamics of biomolecular systems, which could be ideally integrated into molecular dynamics (MD) simulations to accurately determine conformational ensembles of flexible proteins. The applicability of this strategy is hampered by the high computational cost required to calculate scattering intensities from three-dimensional structures. We previously presented a hybrid resolution method that makes atomistic SAXS-restrained MD simulation feasible by adopting a coarse-grained approach to efficiently back-calculate scattering intensities; here, we extend this technique, applying it in the framework of metainference with the aim to investigate the dynamical behavior of flexible biomolecules. The efficacy of the method is assessed on the K63-diubiquitin, showing that the inclusion of SAXS restraints is effective in generating a reliable conformational ensemble, improving the agreement with independent experimental data.

摘要

小角 X 射线散射（SAXS）实验提供了关于生物分子系统动力学的低分辨率但有价值的信息，这些信息可以理想地整合到分子动力学（MD）模拟中，以准确确定柔性蛋白质的构象集合。这种策略的适用性受到从三维结构计算散射强度所需的高计算成本的阻碍。我们之前提出了一种混合分辨率方法，通过采用粗粒化方法来有效地反向计算散射强度，从而使原子 SAXS 约束 MD 模拟成为可行；在这里，我们扩展了这项技术，将其应用于元推断框架中，旨在研究柔性生物分子的动力学行为。该方法在 K63-二泛素的评估中证明了其有效性，表明包含 SAXS 约束条件可以有效地生成可靠的构象集合，提高与独立实验数据的一致性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/7997378/afca2e449c6b/ct9b01181_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/7997378/b7da63d583f8/ct9b01181_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/7997378/50b5a609831a/ct9b01181_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/7997378/58c62996e5c2/ct9b01181_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/7997378/8daf90f0e137/ct9b01181_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/7997378/93f58bc8f168/ct9b01181_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/7997378/afca2e449c6b/ct9b01181_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/7997378/b7da63d583f8/ct9b01181_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/7997378/50b5a609831a/ct9b01181_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/7997378/58c62996e5c2/ct9b01181_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/7997378/8daf90f0e137/ct9b01181_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/7997378/93f58bc8f168/ct9b01181_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/7997378/afca2e449c6b/ct9b01181_0006.jpg

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