Ensemble molecular dynamics for predicting binding energies of DNA intercalators

, although up to 20 replicas could be needed for more flexible ligands that have relatively high degrees of freedom. Overall, MM/PBSA energies estimated from an ensemble of short MD simulations, and corrected for entropy and deformation, are reliable and computationally efficient for ranking and predicting the binding affinity of the cationic intercalators in this study. This method provides a valuable alternative when experimental binding measurements are impractical or costly.