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Updated: Jul 14, 2026

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
Published on: September 20, 2017
A computational model for the prediction of aqueous solubility that includes crystal packing, intrinsic solubility,
Stephen R Johnson1, Xue-Qing Chen, Denette Murphy
1Bristol-Myers Squibb, Co., Princeton, New Jersey 08543, USA. stephen.johnson@bms.com
Abstract:
The optimization of aqueous solubility is an important step along the route to bringing a new therapeutic to market. We describe the development of an empirical computational model to rank the pH-dependent aqueous solubility of drug candidates. The model consists of three core components to describe aqueous solubility. The first is a multivariate QSAR model for the prediction of the intrinsic solubility of the neutral solute. The second facet of the approach is the consideration of ionization using a predicted pKa and the Henderson-Hasselbalch equation. The third aspect of the model is a novel method for assessing the effects of crystal packing on solubility through a series of short molecular dynamics simulations of an actual or hypothetical small molecule crystal structure at escalating temperatures. The model also includes a Monte Carlo error function that considers the variability of each of the underlying components of the model to estimate the 90% confidence interval of estimation.
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