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

RNA. 2018 Sep;24(9):1183-1194. doi: 10.1261/rna.065896.118. Epub 2018 Jun 21.


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 (εin). For predicting the binding affinities, the predictions given by MM/GBSA based on the minimized structures in explicit solvent and the GBGBn1 model with εin = 2 yielded the highest correlation with the experimental data. Moreover, the MM/GBSA calculations based on the minimized structures in implicit solvent and the GBGBn1 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.

Keywords: MM/GBSA; MM/PBSA; binding free energy; docking; protein–RNA interactions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Molecular Docking Simulation / methods*
  • Protein Binding
  • RNA / chemistry
  • RNA / metabolism*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Solvents / chemistry


  • RNA-Binding Proteins
  • Solvents
  • RNA