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Journal Articles Journal of Computational Chemistry Year : 2017

Simple models for nonpolar solvation: Parameterization and testing


Implicit solvent models are important for many biomolecular simulations. The polarity of aqueous solvent is essential and qualitatively captured by continuum electrostatics methods like Generalized Born (GB). However, GB does not account for the solvent-induced interactions between exposed hydrophobic sidechains or solute-solvent dispersion interactions. These "nonpolar" effects are often modeled through surface area (SA) energy terms, which lack realism, create mathematical singularities, and have a many-body character. We have explored an alternate, Lazaridis-Karplus (LK) gaussian energy density for nonpolar effects and a dispersion (DI) energy term proposed earlier, associated with GB electrostatics. We parameterized several combinations of GB, SA, LK, and DI energy terms, to reproduce 62 small molecule solvation free energies, 387 protein stability changes due to point mutations, and the structures of 8 protein loops. With optimized parameters, the models all gave similar results, with GBLK and GBDILK giving no performance loss compared to GBSA, and mean errors of 1.7 kcal/mol for the stability changes and 2 Å deviations for the loop conformations. The optimized GBLK model gave poor results in MD of the Trpcage mini-protein, but parameters optimized specifically for MD performed well for Trpcage and three other small proteins. Overall, the LK and DI nonpolar terms are valid alternatives to SA treatments for a range of applications.
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hal-01955056 , version 1 (14-12-2018)



Eleni Michael, Savvas Polydorides, Thomas Simonson, Georgios Archontis. Simple models for nonpolar solvation: Parameterization and testing. Journal of Computational Chemistry, 2017, 38 (29), pp.2509-2519. ⟨10.1002/jcc.24910⟩. ⟨hal-01955056⟩
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