The results show that, in general, our differentiable MD protocol can systematically optimize the parameter sets, producing models that are in excellent agreement with the reference. In particular, the model produced by differentiable MD for DPPC surpasses the one previously obtained by BO, showing better-peaked distributions for the lipid heads, and improved water penetration at the water/lipid interface, even though the parameters are optimized to be transferable to other lipids in the ∂-HyMD case and were tailored to just DPPC in the BO case. These considerations indicate differentiable MD as a more solid route for the systematic optimization of libraries of compounds.