The SAMPL4 hydration challenge: Evaluation of partial charge sets with explicit-water molecular dynamics simulations

摘要

We used blind predictions of the 47 hydration free energies in the SAMPL4 challenge to test multiple partial charges models in the context of explicit solvent free energy simulations with the GAFF force field. One of the partial charge models, IPolQ-Mod, is a fast continuum solvent-based implementation of the IPolQ approach. The AM1-BCC, RESP and IpolQ-Mod approaches all perform reasonably well (R² > 0.8), while Vcharge, though faster, gives less accurate results (R² of 0.5). The AM1-BCC results are more accurate than those of RESP for tertiary amines and nitrates, but the overall difference in accuracy between these methods is not statistically significant. Interestingly, the IPolQ-Mod method is found to yield partial charges in very close agreement with RESP. This observation suggests that the success of RESP may be attributed to its fortuitously approximating the arguably more rigorous IPolQ approach.