It is well-studied that the differences of the initial conditions among individual simulations lead to rapid divergence of trajectories . Many complex systems hence exhibit sensitive dependence on initial conditions. The calculated thermodynamic properties from individual simulations will therefore inevitably differ. Two sets of ESMACS simulations were performed for the complexes SXX (Table ) independently on Blue Waters and DNAnexus (see the Material and Methods section above). Figure shows the variances and correlation of the calculated binding free energies from the two sets of simulations. Excellent agreement was observed between calculations using two different computational platforms: HPC machine Blue Waters and cloud environment DNAnexus, with a highly significant Spearman correlation of 0.98. No statistical differences were seen between the two sets of calculated binding free energies: 16 out of 20 compounds having identical results, within error bars, and the remaining 4 within two error bars (Figure ). The two simulations produce consistent results, with a mean signed difference of 0.13 kcal/mol and a mean unsigned difference of 0.63 kcal/mol. Both of the calculations have good correlations with the experimental measurement, with correlation coefficients of 0.80 and 0.78 for the simulations on Blue Waters and DNAnexus, respectively. Because of the smaller number of replicas used in the DNAnexus simulations, the error bars in these simulations are ~1.5 times larger than those from Blue Waters simulations. As the two simulations produce similar accuracies, only the results from Blue Waters are reported in the following analyses.