Open ramess101 opened 5 years ago
Yeah, I think this has to be clearer what. MBARR-GCMC doesn't perform poorly, it just doesn't perform as well as it does in liquid. You can't actually do what it does with another method (AFAIK). So it's just a limitation on the method, not a drawback.
@mrshirts @jpotoff @msoroush
This comment actually raises a slightly more complicated issue than I originally thought. This is the paragraph regarding our initial hypothesis:
I feel like our initial hypothesis is somewhat misleading because we can't really compare the overlap of MBAR-ITIC and GCMC-MBAR. In both cases we can quantify overlap with Keff for a different theta than theta_ref. However, MBAR-ITIC Keff is for NVT simulations while GCMC-MBAR is for GC simulations. Furthermore, the state points are completely different: MBAR-ITIC performs NVT simulations along the supercritical temperature (ranging from vapor to liquid like densities) and along compressed liquid isochores. By contrast, GCMC-MBAR performs GC simulations at mu and T conditions that correspond to compressed liquid, near critical point fluid, and rarefied vapor.
The one comparison we can make is how well MBAR-ITIC or GCMC-MBAR predicts saturated vapor or liquid properties for large changes in theta. This comparison clearly demonstrates that GCMC-MBAR is superior. But this is related to the fact that MBAR-ITIC requires reasonable pressure estimates of the liquid phase, which require a large Keff in the compressed liquid isochore state points.
Also, we store two orders of magnitude more configurations in our GCMC-MBAR analysis than in the MBAR-ITIC study.
@mrshirts @jpotoff @msoroush
After thinking about this some more, I guess the best comparison we can make between MBAR-ITIC and GCMC-MBAR is the Keff values at or near saturated liquid. For MBAR-ITIC this corresponds to the lowest temperature on the liquid density isochore, which is simulated directly. For GCMC-MBAR it corresponds to the saturated liquid determined by equating the pressures in the vapor and liquid phases.
The scenario of interest is predicting MiPPE (lam = 16) from configurations sampled with TraPPE (lam = 12). Our previous MBAR-ITIC study reported that Keff is around 1 (i.e., only a single configuration contributes to the average) for the near saturated liquid. By contrast, this study shows that GCMC-MBAR always has a Keff > 1. However, the GCMC-MBAR Keff is still less than 50 for TraPPE -> MiPPE for saturated liquid. Also, GCMC-MBAR starts with about two orders of magnitude more configurations. Although it might seem nice to compare a percent Keff, you cannot really make a percentage Keff comparison because the Keff of 1 is a lower bound, i.e., it is not possible to have Keff < 1.
I think to satisfy this reviewer we just need to state that MBAR-ITIC would have Keff \approx 1 for the saturated liquid state points, while GCMC-MBAR always has Keff > 1.
For the second part of the question, even when GCMC-MBAR has less than 50 in the liquid phase the results for the other properties are still reliable enough that a meaningful optimization is possible for changing lambda.
@mrshirts @jpotoff @msoroush
OK, I think I have made a valid comparison between MBAR-ITIC and GCMC-MBAR, which should satisfy the reviewer and help the reader:
@mrshirts
Could you look over my response and manuscript additions regarding GCMC-MBAR compared with MBAR-ITIC?
@mrshirts @jpotoff @msoroush
Any ideas for what the reviewer intended with the last sentence?
I think there is some confusion regarding MBAR-ITIC, which is understandable since it is not a common method and we only reference it briefly. The whole reason we mention MBAR-ITIC here is to point out that MBAR-ITIC fails miserably when lambda_rr \neq lambda_ref, while GCMC-MBAR is still relatively reliable. But there really is no way to compare MBAR-ITIC and GCMC-MBAR directly because the state points are completely different.
However, I do agree that we need to make it clear that these results support our hypothesis, namely, GCMC-MBAR yields more reliable estimates with greater Keff than MBAR-ITIC for theta_rr \not\approx theta_ref.