This approximation allows the 𝐹 ! atomic , 𝐹 ! solvent , and 𝐹 ! mixed terms to be precalculated separately, regardless of the solvent-specific 𝜌 (and deuteration fraction in the case of SANS). Therefore, in addition to the option of using a buffer other than bulk water, it is possible to assign modified solvation densities to different beads as a proxy for the effect of the solvation layer. More precisely, the 𝜌 value of the beads exposed to the solvent can be adjusted to implicitly include the contribution of the solvation shell. For this purpose, the solvent-accessible surface area (SASA) for each amino acid, nucleotide backbone or base, is calculated on-the-fly during the MD simulation, or only for a single frame, using the efficient LCPO method 54 . Of note, in the case of SANS, the hydrogen -deuterium exchange is also considered. To achieve this result, we have precalculated the three terms of equation ( ) separately for each residue, using both deuterium 𝑓′(𝑞) and hydrogen 𝑓′(𝑞). Only for the beads exposed to the solvent, each time equation ( ) is solved, the terms obtained with deuterium 𝑓′(𝑞) are used instead of those obtained with hydrogen 𝑓′(𝑞), with a probability equal to the deuterium concentration in the buffer. The 𝜌 value, the solvent layer correction parameter, the SASA threshold to consider a residue solvated, as well as the deuterium fraction in SANS, can be defined by the user.