FreeSolv: a database of experimental and calculated hydration free energies, with input files

Abstract

This work provides a curated database of experimental and calculated hydration free energies for small neutral molecules in water, along with molecular structures, input files, references, and annotations. We call this the Free Solvation Database, or FreeSolv. Experimental values were taken from prior literature and will continue to be curated, with updated experimental references and data added as they become available. Calculated values are based on alchemical free energy calculations using molecular dynamics simulations. These used the GAFF small molecule force field in TIP3P water with AM1-BCC charges. Values were calculated with the GROMACS simulation package, with full details given in references cited within the database itself. This database builds in part on a previous, 504-molecule database containing similar information. However, additional curation of both experimental data and calculated values has been done here, and the total number of molecules is now up to 643. Additional information is now included in the database, such as SMILES strings, PubChem compound IDs, accurate reference DOIs, and others. One version of the database is provided in the Supporting Information of this article, but as ongoing updates are envisioned, the database is now versioned and hosted online. In addition to providing the database, this work describes its construction process. The database is available free-of-charge via http://www.escholarship.org/uc/item/6sd403pz.

1.14*CM1A-LBCC: Localized Bond-Charge Corrected CM1A Charges for Condensed-Phase Simulations

“…ΔG hyd was calculated in explicit and implicit water for the 426 molecules collected from the FreeSolv database; 31 full results are provided in the SI. ΔH vap and density were calculated for a subset of molecules at various temperatures, as summarized in the SI.…”

“…In the initial part of this study, the performance of the 1.14*CM1A and 1.20*CM5 charge models with the OPLS-AA force field for a dataset of 426 free energies of hydration 31 was thoroughly examined. The methodology to parameterize the LBCC corrections is discussed, and calculations with the resultant 1.14*CM1A-LBCC charges are found to reduce the error in ΔG hyd by half without affecting the performance for pure liquid properties.…”

Hydration Free Energy as a Molecular Descriptor in Drug Design: A Feasibility Study

“…[47][48][49] Chamberlin et al givea no verview of the experimental methods available to derive DG hyd . [50] Six quantum mechanical methods were investigated using the main stream 6-31 + G(d, p)//6-311 + G(2df,p)b asis set combination.…”

Toward high-throughput predictions of the hydration free energies of small organic molecules from first principles

“…Meanwhile, Mobley et al [86] calculated the hydration free energies of 504 small organic molecules using molecular dynamics (MD) simulations. These simulation results are now available from the FreeSolv database, which includes 643 small organic compounds [87]. The large-scale simulation studies provide fresh insights into the microscopic details of the solvent structure and are invaluable for new theoretical developments.…”