title: Calculation of distribution coefficients in the SAMPL5 challenge from atomic solvation parameters and surface areas.
abstract: In the context of SAMPL5, we submitted blind predictions of the cyclohexane/water distribution coefficient (D) for a series of 53 drug-like molecules. Our method is purely empirical and based on the additive contribution of each solute atom to the free energy of solvation in water and in cyclohexane. The contribution of each atom depends on the atom type and on the exposed surface area. Comparatively to similar methods in the literature, we used a very small set of atomic parameters: only 10 for solvation in water and 1 for solvation in cyclohexane. As a result, the method is protected from overfitting and the error in the blind predictions could be reasonably estimated. Moreover, this approach is fast: it takes only 0.5 s to predict the distribution coefficient for all 53 SAMPL5 compounds, allowing its application in virtual screening campaigns. The performance of our approach (submission 49) is modest but satisfactory in view of its efficiency: the root mean square error (RMSE) was 3.3 log D units for the 53 compounds, while the RMSE of the best performing method (using COSMO-RS) was 2.1 (submission 16). Our method is implemented as a Python script available at https://github.com/diogomart/SAMPL5-DC-surface-empirical .
authors: UCIBIO, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007, Porto, Portugal. diogom@fc.up.pt.
authors: Diogo
authors: 0000-0003-4622-3747
authors: D
authors: Santos-Martins
authors: UCIBIO, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007, Porto, Portugal.
authors: Pedro Alexandrino
authors: PA
authors: Fernandes
authors: UCIBIO, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007, Porto, Portugal.
authors: Maria João
authors: MJ
authors: Ramos
mesh_terms: D003198:Computer Simulation; D003510:Cyclohexanes / Q000737:chemistry*; D055808:Drug Discovery; D008956:Models, Chemical; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D003510:Cyclohexanes; D004364:Pharmaceutical Preparations; D012997:Solvents; D014867:Water; C506365:Cyclohexane
keywords: D3R; Distribution coefficient; Drug design data resource; Free energy of solvation; SAMPL5; Solvent accessible area