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Conformational Ensembles from Experimental Data
and Computer Simulations
Poster Abstracts
154
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.