Small Molecule Solvation Free Energy: Enhanced Conformational Sampling Using Expanded Ensemble Molecular Dynamics...

Area of Science:

• Computational chemistry
• Physical chemistry
• Molecular dynamics simulations

Background:

• Calculating solvation free energy for molecules with complex topologies is challenging.
• Conventional molecular dynamics methods struggle with adequate sampling of functional groups, like ibuprofen's carboxylic acid.

Purpose of the Study:

• To present an efficient expanded ensemble molecular dynamics method for accurate solvation free energy calculations.
• To overcome sampling limitations of conventional methods for molecules with high rotational energy barriers.

Main Methods:

• Development and application of an expanded ensemble molecular dynamics technique.
• Validation through calculation of ibuprofen's solvation free energy in water, methanol, and ethanol.
• Comparison with Bennett's acceptance ratio method for reference calculations.

Main Results:

• The expanded ensemble method significantly enhances conformational sampling and phase space exploration.
• Accurate solvation free energies were obtained for ibuprofen in multiple solvents.
• The method requires only a single simulation and reduces overall simulation time.

Conclusions:

• The expanded ensemble molecular dynamics method is efficient and accurate for solvation free energy calculations.
• It effectively addresses sampling challenges posed by complex molecular topologies and functional groups.
• This approach offers improved performance and reduced computational cost compared to traditional methods.