GAFF/IPolQ-Mod+LJ-Fit: Optimized force field parameters for solvation free energy predictions.

Rational drug design featuring explicit solubility considerations can greatly benefit from molecular dynamics simulations, as they allow for the prediction of the Gibbs free energy of solvation and thus relative solubilities. In our previous work (A. Mecklenfeld, G.

Applicability of a thermodynamic cycle approach for a force field parametrization targeting non-aqueous solvation free energies.

Accurate solvation free energy ΔG predictions require well parametrized force fields. In order to refit Lennard-Jones (LJ) parameters for improved ΔG predictions for a variety of compound classes and chemical environments, a large number of ΔG calculations is required. As the calculation of ΔG is computational expensive, there is need for efficient but precise calculation methods.

Comparison of RESP and IPolQ-Mod Partial Charges for Solvation Free Energy Calculations of Various Solute/Solvent Pairs.

The calculation of solvation free energies ΔG by molecular simulations is of great interest as they are linked to other physical properties such as relative solubility, partition coefficient, and activity coefficient. However, shortcomings in molecular models can lead to ΔG deviations from experimental data. Various studies have demonstrated the impact of partial charges on free energy results.

Round Robin Study: Molecular Simulation of Thermodynamic Properties from Models with Internal Degrees of Freedom.

Thermodynamic properties are often modeled by classical force fields which describe the interactions on the atomistic scale. Molecular simulations are used for retrieving thermodynamic data from such models, and many simulation techniques and computer codes are available for that purpose. In the present round robin study, the following fundamental question is addressed: Will different user groups working with different simulation codes obtain coinciding results within the statistical uncertainty of their data? A set of 24 simple simulation tasks is defined and solved by five user groups working with eight molecular simulation codes: DL_POLY, GROMACS, IMC, LAMMPS, ms2, NAMD, Tinker, and TOWHEE.