Assessing the performance of MM/PBSA and MM/GBSA methods. 8. Predicting binding free energies and poses of protein–RNA complexes

Molecular docking provides a computationally efficient way to predict the atomic structural details of protein–RNA interactions (PRI), but accurate prediction of the three-dimensional structures and binding affinities for PRI is still notoriously difficult, partly due to the unreliability of the existing scoring functions for PRI. MM/PBSA and MM/GBSA are more theoretically rigorous than most scoring functions for protein–RNA docking, but their prediction performance for protein–RNA systems remains unclear. Here, we systemically evaluated the capability of MM/PBSA and MM/GBSA to predict the binding affinities and recognize the near-native binding structures for protein–RNA systems with different solvent models and interior dielectric constants (ε(in)). For predicting the binding affinities, the predictions given by MM/GBSA based on the minimized structures in explicit solvent and the GB(GBn1) model with ε(in) = 2 yielded the highest correlation with the experimental data. Moreover, the MM/GBSA calculations based on the minimized structures in implicit solvent and the GB(GBn1) model distinguished the near-native binding structures within the top 10 decoys for 117 out of the 148 protein–RNA systems (79.1%). This performance is better than all docking scoring functions studied here. Therefore, the MM/GBSA rescoring is an efficient way to improve the prediction capability of scoring functions for protein–RNA systems.