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.
Similar content being viewed by others
References
Eisenberg D, McLachlan AD (1986) Nature 319(6050):199
Boyer RD, Bryan RL (2012) J Phys Chem B 116(12):3772
Wang J, Wang W, Huo S, Lee M, Kollman PA (2001) J Phys Chem B 105(21):5055
Hou T, Qiao X, Zhang W, Xu X (2002) J Phys Chem B 106(43):11295
Ooi T, Oobatake M, Nemethy G, Scheraga HA (1987) Proc Natl Acad Sci 84(10):3086
Pei J, Wang Q, Zhou J, Lai L (2004) Proteins Struct Funct Bioinform 57(4):651
Wang J, Krudy G, Hou T, Zhang W, Holland G, Xu X (2007) J Chem Inf Model 47(4):1395
Kleinjung J, Scott WR, Allison JR, van Gunsteren WF, Fraternali F (2012) J Chem Theory Comput 8(7):2391
Huang SY, Zou X (2010) J Chem Inf Model 50(2):262
Park H (2014) J Comput Aided Mol Des 28(3):175
Mobley DL, Wymer KL, Lim NM, Guthrie JP (2014) J Comput Aided Mol Des 28(3):135
Rustenburg AS, Dancer J, Lin B, Feng JA, Ortwine DF, Mobley DL, Chodera JD (2016) bioRxiv 063081. doi:10.1101/063081
Lin B, Pease JH (2013) Comb Chem High Throughput Screen 16(10):817
Bannan CC, Burley KH, Chiu M, Gilson MK, Mobley DL (2016) J Comput Aided Mol Des (in prep)
Sanner MF, Olson AJ, Spehner JC (1996) Biopolymers 38(3):305
Gasteiger J, Marsili M (1978) Tetrahedron Lett 34:3181
OLBoyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR (2011) J Cheminform 3:33
O’Boyle NM, Morley C, Hutchison GR (2008) Chem Cent J 2(5). doi:10.1186/1752-153X-2-5
Mobley DL, Guthrie JP (2014) J Comput Aided Mol Des 28(7):711
Mobley DL (2013) Experimental and calculated small molecule hydration free energies. Retrieved from http://www.escholarship.org/uc/item/6sd403pz
R Development Core Team (2008) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna. http://www.R-project.org. ISBN 3-900051-07-0
Villa A, Mark AE (2002) J Comput Chem 23(5):548
Marenich AV, Cramer CJ, Truhlar DG (2009) J Phys Chem B 113(18):6378
Acknowledgments
We acknowledge European Union (FEDER funds POCI/01/0145/FEDER/007728) and National Funds (FCT/MEC, Fundação para a Ciência e Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/MULTI/04378/2013.UID/MULTI/04378/2013; NORTE-01-0145-FEDER-000024, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) D.S.M thanks Fundação para a Ciência e Tecnologia for scholarship SFRH/BD/84922/2012.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Santos-Martins, D., Fernandes, P.A. & Ramos, M.J. Calculation of distribution coefficients in the SAMPL5 challenge from atomic solvation parameters and surface areas. J Comput Aided Mol Des 30, 1079–1086 (2016). https://doi.org/10.1007/s10822-016-9951-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10822-016-9951-y