Predicting small-molecule solvation free energies: An informal blind test for computational chemistry

被引：239

作者：

Nicholls, Anthony ^{[1
]}

Mobley, David L. ^{[2
]}

Guthrie, J. Peter ^{[3
]}

Chodera, John D. ^{[4
]}

Bayly, Christopher I. ^{[5
]}

Cooper, Matthew D. ^{[5
]}

Pande, Vijay S. ^{[4
]}

机构：

[1] OpenEye Sci Software Inc, Santa Fe, NM 87508 USA

[2] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA

[3] Univ Western Ontario, Dept Chem, London, ON N6A 5B7, Canada

[4] Stanford Univ, Dept Chem, Stanford, CA 94305 USA

[5] Merck Frosst Canada Ltd, Kirkland, PQ H9H 3L1, Canada

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 04期

关键词：

D O I：

10.1021/jm070549+

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Experimental data on the transfer of small molecules between vacuum and water are relatively sparse. This makes it difficult to assess whether computational methods are truly predictive of this important quantity or merely good at explaining what has been seen. To explore this, a prospective test was performed of two different methods for estimating solvation free energies: an implicit solvent approach based on the Poisson-Boltzmann equation and an explicit solvent approach using alchemical free energy calculations. For a set of 17 small molecules, root mean square errors from experiment were between 1.3 and 2.6 kcal/mol, with the explicit solvent free energy approach yielding somewhat greater accuracy but at. greater computational expense. Insights from outliers and suggestions for future prospective challenges of this kind are presented.

引用

页码：769 / 779

页数：11

共 74 条

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