Small molecule hydration energy and entropy from 3D-RISM.

Area of Science:

• Computational chemistry
• Physical chemistry
• Molecular modeling

Background:

• Implicit solvent models simplify solvent environment calculations for solutes.
• Assessing model accuracy involves comparing computed gas-to-liquid transfer free energies with experimental data.
• Temperature dependence of solvation provides deeper insights into implicit solvent model performance.

Purpose of the Study:

• To compute temperature derivatives of hydration free energies using the 3D-RISM integral equation approach.
• To evaluate the accuracy of implicit solvent models for a large set of drug-like molecules.
• To investigate the effectiveness of linear correction schemes for hydration free energies.

Main Methods:

• Utilized the 3D-RISM integral equation theory to calculate hydration free energies.
• Computed temperature derivatives of hydration free energies for 1123 small molecules.
• Calculated hydration energies and entropies for 74 molecules and compared with experimental data.

Main Results:

• Direct 3D-RISM hydration free energies showed poor agreement with experimental values.
• Previously proposed linear correction schemes significantly improved agreement with experimental hydration free energies.
• These corrections also yielded good agreement for hydration energies and entropies, with minor modifications.

Conclusions:

• Linear correction schemes are effective in improving the accuracy of 3D-RISM for hydration free energies.
• The corrected 3D-RISM approach provides reliable predictions for hydration energies and entropies.
• This work highlights the importance of corrections for accurate solvation free energy predictions in computational chemistry.