کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5915058 1162771 2010 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Automated multi-model reconstruction from single-particle electron microscopy data
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Automated multi-model reconstruction from single-particle electron microscopy data
چکیده انگلیسی

Biological macromolecules can adopt multiple conformational and compositional states due to structural flexibility and alternative subunit assemblies. This structural heterogeneity poses a major challenge in the study of macromolecular structure using single-particle electron microscopy. We propose a fully automated, unsupervised method for the three-dimensional reconstruction of multiple structural models from heterogeneous data. As a starting reference, our method employs an initial structure that does not account for any heterogeneity. Then, a multi-stage clustering is used to create multiple models representative of the heterogeneity within the sample. The multi-stage clustering combines an existing approach based on Multivariate Statistical Analysis to perform clustering within individual Euler angles, and a newly developed approach to sort out class averages from individual Euler angles into homogeneous groups. Structural models are computed from individual clusters. The whole data classification is further refined using an iterative multi-model projection-matching approach. We tested our method on one synthetic and three distinct experimental datasets. The tests include the cases where a macromolecular complex exhibits structural flexibility and cases where a molecule is found in ligand-bound and unbound states. We propose the use of our approach as an efficient way to reconstruct distinct multiple models from heterogeneous data.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Structural Biology - Volume 170, Issue 1, April 2010, Pages 98-108
نویسندگان
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