While there were differences between the molecular dynamics and uESE results presented in the manuscript, both lead to the same result that vitamin D2 and D3 have a relatively poor aqueous solubility as a result of unfavorable process of carving a cavity in solution. For the case of water, this would involve disrupting water's hydrogen bond network which includes overcoming favorable water-water hydrogen bonds. The advantage of using uESE is we can readily perform calculations in water and 91 organic solvents with significantly less computational cost. In the supporting information accompanying the electronic version of this manuscript, we have tabulated the total solvation-free energy and its contributions for vitamin D2 and D3 in all 92 solvents computed using uESE.