Karmakar et al. , compute the nucleation barrier at two distinct supersaturation conditions from unseeded simulations (see section 4.2 and Figure ) by coupling WTmetaD with C𝜇MD . This approach allows a decoupling of the size of the nucleus from the chemical potential of the parent phase by mimicking an open boundary system at constant composition, therefore overcoming the depletion issues that typically affect both the qualitative and quantitative behaviour of nucleating systems in small volumes (see section 3.2) . Depletion artefacts affect the shape of the nucleation free energy profile, the estimate of the critical nucleus size, and in severe cases, can even completely inhibit nucleation. Depletion effects are also present in regular seeding simulations. However, depletion only affects the estimate of nucleation rates when the critical nucleus size 𝑛 * << 𝑉 (𝑐 -𝑐 𝑠𝑎𝑡 ) , where 𝑐 𝑠𝑎𝑡 is the concentration of a saturated solution. For systems where 𝑐 𝑠𝑎𝑡 is large, satisfying this equation may require very large simulation volumes.