Extending the Einstein crystal method to molecular constraints with an outlook on drug discovery
DOI: 10.1063/1.5111761
Extending the Einstein crystal method to molecular constraints with an outlook on drug discovery lead image
Predicting solubilities for molecular compounds has important practical applications and theoretical significance. For instance, the aqueous solubility of a drug could affect the bioavailability, and therefore, its effectiveness, and the solubility of a drug in different solvents has a dramatic impact on formulation development and the manufacturing process.
In efforts to predict solubilities for a wider range of molecules, Gobbo et al. extended and applied a generalized Einstein crystal method (ECM) with a specific focus on pharmaceutical applications.
The ECM was developed in the 1980s to compute the solubility of simple atomic crystals, such as sodium chloride. More recently, researchers have extended the method to compute the solubility of molecules, but focusing on sparingly soluble ones.
The researchers behind the latest paper have previously extended the ECM method to include molecules with higher solubility levels and strongly polar molecules. Their latest study takes another step further to also include molecular systems subject to constraints, an important aspect of efficient molecular simulations.
They showed that if constraints are applied independently on the different molecules, the contribution of momenta and intramolecular degrees of freedom to the chemical potentials can be kept implicit in the mathematical derivation. This allows for a fundamental simplification in the calculations, similar to the case of molecular systems without constraints.
“The result is that we have substantially widened the class of models to which the method can be applied,” author Gianpaolo Gobbo said. “We have shown that, although the derivation changes, the procedure is exactly the same for molecular systems subject to constraints.”
Source: “On computing the solubility of molecular systems subject to constraints using the extended Einstein crystal method,” by Gianpaolo Gobbo, Giovanni Ciccotti, and Bernhardt L. Trout, The Journal of Chemical Physics (2019). The article can be accessed at https://doi.org/10.1063/1.5099378 .
