title: Predicting small-molecule solvation free energies: an informal blind test for computational chemistry.
abstract: 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.
authors.affiliation: OpenEye Scientific Software, Inc., Santa Fe, New Mexico 87508,USA. anthony@eyesopen.com
authors.forename: Anthony
authors.initials: A
authors.lastname: Nicholls
authors.forename: David L
authors.initials: DL
authors.lastname: Mobley
authors.forename: J Peter
authors.initials: JP
authors.lastname: Guthrie
authors.forename: John D
authors.initials: JD
authors.lastname: Chodera
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Bayly
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Cooper
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Pande
mesh_terms: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008956:Models, Chemical; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents