Atomistic-scale simulations are prominent scientific applications that require the repetitive execution of a computationally expensive routine to calculate a system’s potential energy. Prior work shows that these expensive routines can be replaced with a machine-learned surrogate approximation to accelerate the simulation at the expense of the overall accuracy. The exact balance of speed and accuracy depends on the specific configuration of the surrogate-modeling workflow and the science itself, and prior work leaves it up to the scientist to find a configuration that delivers the required accuracy for their science problem. Unfortunately, due to the underlying system dynamics, it is rare that a single surrogate configuration presents an optimal accuracy/latency trade-off for the entire simulation. In practice, scientists must choose conservative configurations so that accuracy is always acceptable, forgoing possible acceleration. As an alternative, we propose Proxima, a systematic and automated method for dynamically tuning a surrogate-modeling configuration in response to real-time feedback from the ongoing simulation. Proxima estimates the uncertainty of applying a surrogate approximation in each step of an iterative simulation. Using this information, the specific surrogate configuration can be adjusted dynamically to ensure maximum speedup while sustaining a required accuracy metric. We evaluate Proxima using a Monte Carlo sampling application and find that Proxima respects a wide range of user-defined accuracy goals while achieving speedups of 1.02–5.5X relative to a standard