Predicting Ligand-Protein Binding Affinities with the MOE MM/GBVI Method
Using MOE's NAMD interface and a custom SVL script to perform MM/GBVI on protein-ligand complexes, studies have been performed on a number of systems. Simulations were performed using the Amber10:EHT force field and AM1-BCC partial charges for the ligand. The results have been compared with literature MM/GBSA studies and show a small benefit in using the GBVI solvation method, which has also been shown to be computationally faster. The studies show the necessity of using molecular dynamics simulations to sample the conformational space of the complex and of running replicate simulations for each protein-ligand complex to achieve better accuracy. Typically, identical simulations show a standard deviation of ~3-4 kcal.mol-1. The effects of varying the internal protein dielectric have also been investigated and show that the choice of dielectric is less system specific when using MM/GBVI, with a preferred value of 1.0.