Projects per year
Abstract
We demonstrate that the intrinsic aqueous solubility of crystalline druglike molecules can be estimated with reasonable accuracy from sublimation free energies calculated using crystal lattice simulations and hydration free energies calculated using the 3D Reference Interaction Site Model (3DRISM) of the Integral Equation Theory of Molecular Liquids (IET). The solubilities of 25 crystalline druglike molecules taken from different chemical classes are predicted by the model with R = 0.85 and RMSE = 1.45 log10 S units, which is significantly more accurate than results obtained using implicit continuum solvent models. The method is not directly parameterized against experimental solubility data and it offers a full computational characterization of the thermodynamics of transfer of the drug molecule from crystal phase to gas phase to dilute aqueous solution.
Original language | English |
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Pages (from-to) | 3322–3337 |
Number of pages | 16 |
Journal | Journal of Chemical Theory and Computation |
Volume | 8 |
Issue number | 9 |
Early online date | 25 Jul 2012 |
DOIs | |
Publication status | Published - 11 Sep 2012 |
Keywords
- solubility
- RISM
- hydration
- sublimation
- crystal
- first-principles
- ab initio
- drug discovery
- bioavailability
- pharmacokinetics
- first principles
- calculation
- intrinsic aqueous solubility
- crystalline
- druglike molecules
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Projects
- 1 Active
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Investigating the accuracy of sublimation free energy prediction by ab initio and semi-empirical methods.
Palmer, D., Fedorov, M., Mitchell, J., van Mourik, T. & McDonagh, J.
1/01/13 → …
Project: Research
Equipment
Research Output
- 56 Citations
- 3 Speech
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Computational biomolecular design using the integral equation theory of molecular liquids: from drug discovery to bionanotechnology
Palmer, D., 4 Mar 2015.Research output: Contribution to conference › Speech
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Solvation thermodynamics of biomolecules from the integral equation theory of molecular liquids
Palmer, D., Misin, M. & Fedorov, M., 20 Aug 2014, (Unpublished).Research output: Contribution to conference › Speech
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Computing intrinsic aqueous solubility of crystalline organic molecules
Palmer, D. & Fedorov, M., 4 Sep 2013.Research output: Contribution to conference › Speech
Activities
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Computational Biomolecular Design using the Integral Equation Theory of Molecular Liquids: from Drug Discovery to Bionanotechnology
David Palmer (Contributor)
27 Apr 2015Activity: Talk or presentation types › Invited talk
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WE-Heraeus Seminar on "Exploring Solvation Science"
David Palmer (Participant)
27 Oct 2014 → 30 Oct 2014Activity: Participating in or organising an event types › Participation in conference