Structural Characterization of Protein–Protein Complexes by Integrating Computational Docking with Small-angle Scattering Data

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• 作者：Carles Pons ; Marco D’ ; Abramo ; Dmitri I. Svergun ; Modesto Orozco ; Pau Bernadó ; Juan Ferná ; ndez-Recio
• 关键词：protein– ; protein interactions ; docking ; small-angle X-ray scattering ; protein complex structure ; binding energy
• 刊名：Journal of Molecular Biology
• 出版年：2010
• 出版时间：22 October 2010
• 年：2010
• 卷：403
• 期：2
• 页码：217-230
• 全文大小：789 K

文摘

X-ray crystallography and NMR can provide detailed structural information of protein–protein complexes, but technical problems make their application challenging in the high-throughput regime. Other methods such as small-angle X-ray scattering (SAXS) are more promising for large-scale application, but at the cost of lower resolution, which is a problem that can be solved by complementing SAXS data with theoretical simulations. Here, we propose a novel strategy that combines SAXS data and accurate protein–protein docking simulations. The approach has been benchmarked on a large pool of known structures with synthetic SAXS data, and on three experimental examples. The combined approach (pyDockSAXS) provided a significantly better success rate (43 % for the top 10 predictions) than either of the two methods alone. Further analysis of the influence of different docking parameters made it possible to increase the success rates for specific cases, and to define guidelines for improving the data-driven protein–protein docking protocols.