X-ray Solution scattering is a routine biophysical technique used to determine structure and dynamics of macromolecules in solution. When solution scattering data is interpreted, often with the aid of known atomic models, an improved understanding of the macromolecule's biological function and properties emerges. The main challenge associated with solution scattering data is the intrinsic lack of information that can be obtained from solution scattering curves. By performing the solution scattering experiment at the femtosecond time scale by using a free-electron laser, the information content of the data can be significantly enhanced, leading to fewer ambiguities in derived structural models and a better understanding of the associated biology. This technique is called fluctuation scattering. The current understanding of fluctuation scattering theory, optimal data analyses and model reconstructing practices is limited, while the availability of user facilities on which these experiments can be performed is growing rapidly. Further development in data reduction, model generation and basic theory will lead to a mature biophysical technique providing the structural biology community with information-dense solution scattering data. The proposed development of theory, data reduction and analyses methods will ultimately result in a better understanding of biological systems at the atomic level.

Public Health Relevance

In order to understand complex biological systems at the molecular level, a wide variety of experimental techniques has to be employed in order to obtain a complete description of the system under study. The technique that we propose to develop will provide information-dense data from macromolecules in a near native environment and will result in a deeper understanding of the living cell.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM109019-01A1
Application #
8720476
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Swain, Amy L
Project Start
2014-06-01
Project End
2019-02-28
Budget Start
2014-06-01
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$346,180
Indirect Cost
$156,180
Name
Lawrence Berkeley National Laboratory
Department
Type
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720