Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

117-POS Board 37 Determining Structural Ensembles of Flexible Biomolecules Using Small-angle X-ray Scattering and Computer Simulations

Junhui Peng, Yonghui Zhang, Bin Wen, Peng Cheng, Zhiyong Zhang . University of Science and Technology of China, Hefei, Anhui, China.

Large biomolecules, such as proteins, RNA, DNA, and their complexes, are generally flexible with large scale conformational changes in solution, which are closely related to their biological functions. Small-angle X-ray scattering (SAXS) has made substantial progress over the past decades and has become more and more popular among structural biologists. SAXS is particularly useful in characterizing the flexibility of a large biomolecule because the scattering profile contains the information of multiple conformations of the biomolecule and their relative population in solution. In recent years, a notion of ‘integrative structural biology’ has been proposed, which aims to determine the biomolecular structure and characterize its flexibility by combining complementary high and low resolution experimental data using computer simulations. Our work focus on the development and application of multi-scale computer simulation methods integrating SAXS and other structural data to investigate conformational dynamics of large biomolecules. we have determined structural ensembles of several multi- domain proteins and protein complexes by integrating SAXS data into various simulation techniques, such as all-atom molecular dynamics simulations, enhanced sampling techniques, and coarse-grained modeling. We have also developed a couple of new computational tools, which aim to (1) easily integrate any low-resolution structural data including SAXS to construct atomic models of large biomolecules, and (2) efficiently perform SAXS-oriented ensemble refinement for flexible biomolecules. Multi-scale simulations integrating SAXS data have enabled us to characterize conformational changes of large biomolecules and their assemblies accurately, which contributes to the study of the relation between structural dynamics and biological function.

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