Even when using the Martini representation to determine the scattering intensity with hySAXS, the study of relatively large systems can be challenging. Furthermore, this approach was not designed to account for possible corrections due to solvation layer effects. Here we present a novel hySAS method for proteins and nucleic acids that is faster, more accurate with the inclusion of a solvent layer contribution and extended to the calculation of SANS intensity. As a case study, we applied the hySAS approach to determine the conformational ensemble of human gelsolin (GSN). This 83 kDa protein (reviewed by Nag et al. ) is composed of six homologous domains (named G1 to G6) connected by flexible linker regions, and is considered a master regulator of actin dynamics thanks to its severing and capping activities . GSN and the other members of the superfamily play an important role in several physiological processes, such as cell division and mobility, trafficking, signal transduction, immunomodulation, and inflammation . GSN is also responsible for a hereditary amyloidosis and it is involved in several other diseases, particularly cancer (reviewed by Li et al. ). Each GSN domain harbours a Ca 2+ binding site and binding to the ion triggers local changes and domain rearrangements which shift the protein from a closed to an open conformation . In the absence of Ca 2+ , the actin binding sites are buried, limiting the ability of GSN to interact with actin filaments. In this inactive state, GSN can be crystallised , but resolution is relatively low and several stretches of the protein are too flexible to be modelled; such flexibility has been shown to be relevant for GSN physiopathology . In this work, we have determined the ensemble of gelsolin structures in the closed/inactive state using SAXS data measured in the absence of calcium. Furthermore, as a second example of the applicability of hySAS, we refined a previously published protein-RNA complex. This newly introduced hySAS, as well as our previous implementations, are already available in the ISDB 51 module of the PLUMED software, an open-source software designed to enhance and extend various MD engines or to be used as a stand-alone package to perform a wide range of advanced analysis of complex biomolecular systems.