摘要 : We developed and implemented an ensemblerefinement method to study dynamic biomolecular assemblies with intrinsically disordered segments. Data from small angle X-ray scattering (SAXS) experiments and from coarse-grained molecular... 展开 We developed and implemented an ensemblerefinement method to study dynamic biomolecular assemblies with intrinsically disordered segments. Data from small angle X-ray scattering (SAXS) experiments and from coarse-grained molecular simulations were combined by using a maximum-entropy approach. The method was applied to CHMP3 of ESCRT-III, a protein with multiple helical domains separated by flexible linkers. Based on recent SAXS data by Lata et al. (J. Mol. Biol. 378, 818, 2008), we constructed ensembles of CHMP3 at low- and high-salt concentration to characterize its closed autoinhibited state and open active state. At low salt, helix a_5 is bound to the tip of helices a_1 and a_2, in excellent agreement with a recent crystal structure. Helix a_6 remains free in solution and does not appear to be part of the autoinhibitory complex. The simulation-based ensemble refinement is general and effectively increases the resolution of SAXS beyond shape information to atomically detailed structures. 收起