ArticleJournal of chemical theory and computation2012
The Structure, Thermodynamics and Solubility of Organic Crystals from Simulation with a Polarizable Force Field.
Article in Journal of chemical theory and computation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Physics-Based Solubility Prediction for Organic Molecules.Chemical reviews · 2025Review
- Fine-tuning molecular mechanics force fields to experimental free energy measurements.bioRxiv : the preprint server for biology · 2025Article
- Force Field X: A computational microscope to study genetic variation and organic crystals using theory and experiment.The Journal of chemical physics · 2024Article
- Crystal Polymorph Search in theCrystal growth & design · 2024Article
- Constant-pH Simulations with the Polarizable Atomic Multipole AMOEBA Force Field.Journal of chemical theory and computation · 2024Article
- Low-Frequency Raman Spectroscopy of Pure and Cocrystallized Mycophenolic Acid.Pharmaceutics · 2023Article
- Performing solvation free energy calculations in LAMMPS using the decoupling approach.Journal of computer-aided molecular design · 2020Article
- A Polarization-Consistent Model for Alcohols to Predict Solvation Free Energies.Journal of chemical information and modeling · 2020Article
- Scalable Indirect Free Energy Method Applied to Divalent Cation-Metalloprotein Binding.Journal of chemical theory and computation · 2019Article
- Computational insights into the binding of IN17 inhibitors to MELK.Journal of molecular modeling · 2019Article
- Polarizable Force Fields for Biomolecular Simulations: Recent Advances and Applications.Annual review of biophysics · 2019Review
- Molecular simulation as a computational pharmaceutics tool to predict drug solubility, solubilization processes and partitioning.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2019Review
- Tinker 8: Software Tools for Molecular Design.Journal of chemical theory and computation · 2018Article
- AMOEBA Polarizable Atomic Multipole Force Field for Nucleic Acids.Journal of chemical theory and computation · 2018Article
- Computational prediction of drug solubility in water-based systems: Qualitative and quantitative approaches used in the current drug discovery and development setting.International journal of pharmaceutics · 2018Review
- Challenges in the use of atomistic simulations to predict solubilities of drug-like molecules.F1000Research · 2018Article
- A Polarizable Atomic Multipole-Based Force Field for Molecular Dynamics Simulations of Anionic Lipids.Molecules (Basel, Switzerland) · 2017Article
- Ionic Solution: What Goes Right and Wrong with Continuum Solvation Modeling.The journal of physical chemistry. B · 2017Article
- Mapping the Drude polarizable force field onto a multipole and induced dipole model.The Journal of chemical physics · 2017Article
- Tinker-OpenMM: Absolute and relative alchemical free energies using AMOEBA on GPUs.Journal of computational chemistry · 2017Article
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7 authors.
Funding
Abstract
An important unsolved problem in materials science is prediction of the thermodynamic stability of organic crystals and their solubility from first principles. Solubility can be defined as the saturating concentration of a molecule within a liquid solvent, where the physical picture is of solvated molecules in equilibrium with their solid phase. Despite the importance of solubility in determining the oral bioavailability of pharmaceuticals, prediction tools are currently limited to quantitative structure-property relationships that are fit to experimental solubility measurements. For the first time, we describe a consistent procedure for the prediction of the structure, thermodynamic stability and solubility of organic crystals from molecular dynamics simulations using the polarizable multipole AMOEBA force field. Our approach is based on a thermodynamic cycle that decomposes standard state solubility into the sum of solid-vapor sublimation and vapor-liquid solvation free energies [Formula: see text], which are computed via the orthogonal space random walk (OSRW) sampling strategy. Application to the n-alkylamides series from aeetamide through octanamide was selected due to the dependence of their solubility on both amide hydrogen bonding and the hydrophobic effect, which are each fundamental to protein structure and solubility. On average, the calculated absolute standard state solubility free energies are accurate to within 1.1 kcal/mol. The experimental trend of decreasing solubility as a function of n-alkylamide chain length is recapitulated by the increasing stability of the crystalline state and to a lesser degree by decreasing favorability of solvation (i.e. the hydrophobic effect). Our results suggest that coupling the polarizable AMOEBA force field with an orthogonal space based free energy algorithm, as implemented in the program Force Field X, is a consistent procedure for predicting the structure, thermodynamic stability and solubility of organic crystals.
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