title: Predicting hydrophobic solvation by molecular simulation: 1. Testing united-atom alkane models.
abstract: We present a systematic test of the performance of three popular united-atom force fields-OPLS-UA, GROMOS and TraPPE-at predicting hydrophobic solvation, more precisely at describing the solvation of alkanes in alkanes. Gibbs free energies of solvation were calculated for 52 solute/solvent pairs from Molecular Dynamics simulations and thermodynamic integration making use of the IBERCIVIS volunteer computing platform. Our results show that all force fields yield good predictions when both solute and solvent are small linear or branched alkanes (up to pentane). However, as the size of the alkanes increases, all models tend to increasingly deviate from experimental data in a systematic fashion. Furthermore, our results confirm that specific interaction parameters for cyclic alkanes in the united-atom representation are required to account for the additional excluded volume within the ring. Overall, the TraPPE model performs best for all alkanes, but systematically underpredicts the magnitude of solvation free energies by about 6% (RMSD of 1.2 kJ/mol). Conversely, both GROMOS and OPLS-UA systematically overpredict solvation free energies (by ∼13% and 15%, respectively). The systematic trends suggest that all models can be improved by a slight adjustment of their Lennard-Jones parameters. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Chemical and Process Engineering, University of Strathclyde, 75 Montrose Street, Glasgow, G1 1XJ, United Kingdom.
authors.forename: Miguel
authors.identifier: 0000-0003-3009-4725
authors.initials: M
authors.lastname: Jorge
authors.affiliation: LSRE - Laboratory of Separation and Reaction Engineering - Associate Laboratory LSRE/LCM, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, Porto, 4200-465, Portugal.
authors.forename: Nuno M
authors.initials: NM
authors.lastname: Garrido
authors.affiliation: Chemistry Department and Coimbra Chemistry Centre, Faculty of Science and Technology, University of Coimbra, Coimbra, 3004-535, Portugal.|BSIM2 - Drug Discovery, Parque Tecnológico de Cantanhede, Cantanhede, 3060-197, Portugal.
authors.forename: Carlos J V
authors.initials: CJ
authors.lastname: Simões
authors.affiliation: Chemistry Department and Coimbra Chemistry Centre, Faculty of Science and Technology, University of Coimbra, Coimbra, 3004-535, Portugal.|Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3004-504, Portugal.
authors.forename: Cândida G
authors.initials: CG
authors.lastname: Silva
authors.affiliation: Chemistry Department and Coimbra Chemistry Centre, Faculty of Science and Technology, University of Coimbra, Coimbra, 3004-535, Portugal.|Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3004-504, Portugal.
authors.forename: Rui M M
authors.initials: RM
authors.lastname: Brito
keywords: force field; free energy; molecular simulation; non-polar; solubility