We obtain a p-value of ≥ 0.05 for only 3 out of the 45 pairs of replicas (∼ 6.67%). Thus, 42 pairs (∼ 93.33%) indeed sample non-identical regions of phase space. Table contains relevant statistics (as discussed above for the ADRP system) for all systems which shows that the variability across replicas is prominent in all systems studied without exception at the microsecond timescale. The above findings establish beyond doubt the non-reproducibility of long trajectories for moderately sized protein-ligand systems at least for simulations of duration up to 10 microseconds. They confirm that it is far-fetched to draw final conclusions on the true nature of a system from an individual MD simulation as two independent trajectories would sample different regions of the phase space for reasonbly long temporal durations when Figure : Cumulative density functions (CDFs) of the contact frequency distributions for all "long" replicas (dashed lines) as well as concatenated splitting protocol trajectories (solid line) for ADRP-tofacitinib system. The width of the p-box so generated indicates the extent of variability across "long" replicas compared against the splitting protocol.