Predicting Small-Molecule Solvation Free Energies: An Informal Blind Test for Computational Chemistry

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• 作者：Anthony Nicholls ; David L. Mobley ; J. Peter Guthrie ; John D. Chodera ; Christopher I. Bayly ; Matthew D. Cooper ; Vijay S. Pande
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：February 28, 2008
• 年：2008
• 卷：51
• 期：4
• 页码：769 - 779
• 全文大小：1587K
• 年卷期：v.51,no.4(February 28, 2008)
• ISSN：1520-4804

文摘

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.