To assess the extent of energy drift, we performed 100 ns NVE ensemble simulations of both cAMP and ethane molecular systems. These simulations explored four distinct combinations of applying and omitting HMR and SHAKE constraints (results summarized in Table ). A critical observation was the instability of simulations lacking SHAKE constraints at timesteps of 2, 2.5, 3.3333, and 4 fs. This instability prevented any further investigation of these parameter combinations, highlighting the crucial role of SHAKE in maintaining simulation integrity at these timesteps.