Definition of the spherical coordinate system. This system is used to describe the center-of-mass (COM) position of the Sc substrate with respect to the Na2 in vSGLT. Thus, the Na2 position is defined as the reference point (0,0,0). The x,y,z directions shown are based on the reoriented coordinates of PDB code 3DH4 from the Orientations of Proteins in Membranes (OPM) database (53), which have the z axis perpendicular to the membrane, and the x axis largely pointing from Na2 to the side chain of Tyr-263. The projection of the COM on the xy plane is shown as the point COMxy. “r” is the distance between Na2 and COM; “θ” is the angle between the x axis and the line connecting Na2-COMxy, and “ϕ” is the angle between the z axis and the line connecting Na2-COM.