The first term represents the physical force. For the pairwise terms U ele and U vdw this force acts along the vector connecting the two atoms involved. The second term represents a so-called drift force. It is only relevant for solvent molecules in regions where s varies, and acts in the direction of the s-gradient. Expressions for the forces associated with the terms of Eqs. ( )-( ) are provided in Suppl. Mat. Section S1.1.