We also analyzed the constraint topologies of the Martini 3 small molecule library for the highest λ max , and we performed explicit simulations for the three molecules with the largest eigenvalues λ max that corroborated the eigenvalue analysis. Overall, even for the largest λ max = 0.76 we did not observe appreciable temperature gradients. The analysis and optimization method presented here can be readily incorporated into automatic topology builders and is potentially useful for other constrained molecules as well as rigid body simulations.