DENSS-multiple: A structure reconstruction method using contrast variation of small-angle neutron scattering based on the DENSS algorithm

The 3D structure of biomacromolecules, such as protein and DNA/RNA, provide keys to understanding their biological functions. Among many structural biology techniques, small-angle scattering techniques with ab initio methods have been widely used to reveal biomolecular structures in relevant solution conditions. Recently, a method called DENsity from Solution Scattering (DENSS) was developed to reconstruct the scattering density directly from biological small-angle X-ray and neutron scattering data instead of using a dummy atom modeling approach. Here, a method named DENSS-Multiple was developed to work simultaneously on multiple datasets from small-angle neutron scattering (SANS) contrast variation data. The easily manipulable neutron contrast has been widely exploited to study the structure and function of biological macromolecules and their complexes in solution. This new method provides a single structural result that includes all the information represented by different contrasts from SANS. The results from DENSS-Multiple generally have better resolution than those from DENSS, and more subtle features are represented by density variations from different phases of a structure. DENSS-Multiple was tested on various examples, including simulated and experimental data. These results, along with DENSS-Multiple's applications and limitations, are discussed herein.