Projects per year
Abstract
We report the results of testing Quantitative Structure-Property Relationships (QSPR) that were trained upon the same druglike molecules but two different sets of solubility data: (i) data ex- tracted from several different sources from the published literature, for which the experimental uncertainty is estimated to be 0.6-0.7 log S units (referred to mol/l); (ii) data measured by a sin- gle accurate experimental method (CheqSol), for which experimental uncertainty is typically < 0.05 log S units. Contrary to what might be expected, the models derived from the CheqSol experimental data are not more accurate than those derived from the “noisy” literature data. The results suggest that, at the present time, it is the deficiency of QSPR methods (algorithms and/or descriptor sets), and not, as is commonly quoted, the uncertainty in the experimen- tal measurements, which is the limiting factor in accurately predicting aqueous solubility for pharmaceutical molecules.
Original language | English |
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Pages (from-to) | 2962–2972 |
Number of pages | 11 |
Journal | Molecular Pharmaceutics |
Volume | 11 |
Issue number | 8 |
Early online date | 9 Jul 2014 |
DOIs | |
Publication status | Published - 4 Aug 2014 |
Keywords
- pharmaceutical
- rule-of-five
- solubility
- bioavailability
- QSPR
- QSAR
- druglike
- ADME
- Random Forest
- dissolution
- experimental error
- CheqSol
- Noyes−Whitney
- Henderson−Hasselbalch
- polymorph
- crystal
- machine learning
- general solubility equation
- ADMET
Profiles
Projects
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Fast and Accurate Predictions of Physical-Chemical Properties of Bioactive Molecules
1/05/14 → …
Project: Research
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IETSOL: CALCULATION OF PHARMACOKINETIC PROPERTIES OF DRUGLIKE MOLECULES USING INTEGRAL EQUATION THEORY
Palmer, D. & Fedorov, M.
1/02/12 → 31/01/14
Project: Research Fellowship
Equipment
Research Output
- 54 Citations
- 2 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
Prizes
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Chemical Structures Association Trust Grant
Palmer, David (Recipient), 2 Jun 2014
Prize: Prize (including medals and awards)
Activities
- 1 Invited talk
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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