Chemistry Reference
In-Depth Information
6. The KBIs are most sensitive to the accuracy of the activity data used during
the analysis, and least sensitive to the accuracy of the compressibility data.
Often it is even assumed that the compressibility of the solution is ideal, and
this is a reasonable assumption in the absence of real compressibility data
as is the use of isentropic compressibility data (Matteoli and Lepori 1984).
Compressibility uncertainties as high as 50% have been shown to have insig-
nificant effects on the values of the KBIs (Matteoli and Lepori 1984).
7. The KBIs should reach a plateau value at the distance that the RDFs tend
toward unity. Although the procedure for choosing a distance over which
to take the average of the KBIs is somewhat arbitrary, it is able to capture
the significant differences in the degree of molecular association between
different FFs.
8. Although in theory there should be multiple RDFs that, upon integration,
could provide the same value of
G
ij
, and thus multiple solutions to the
charge distribution, we have never found this to be a practical concern. In
fact, it has been difficult to find one set of partial charges (or one set of
RDFs), which reasonably reproduce the three KBIs.
In our opinion, the results presented here clearly show that conventional FFs can
possess a significant imbalance of solute solvation and self-association in solutions.
Fortunately, this problem can be overcome by adjusting the effective molecular
charge distributions of the solutes during the parameterization procedure. In our
opinion, the KBFF models represent an often dramatic improvement over the cur-
rently used protein FFs and should be seriously considered if one wishes to study
conformational or association equilibria with reasonable accuracy.
ACKNOWLEDGMENTS
The project described was supported by grant R01GM079277 to Paul E. Smith from
the National Institute of General Medical Sciences and grants DGE-0841414 and
DGE-0750823 from the National Science Foundation to Elizabeth A. Ploetz. The
content is solely the responsibility of the authors and does not necessarily represent
the official views of the National Institute of General Medical Sciences, the National
Institutes of Health, or the National Science Foundation.
