A Python tool to set up relative free energy calculations in GROMACS

Area of Science:

• Computational chemistry
• Molecular dynamics simulations
• Free energy calculations

Background:

• Molecular dynamics (MD) simulations are crucial for free energy calculations, but their setup is often complex and manual.
• Existing MD packages typically lack automated setup functionalities, particularly for relative free energy calculations.
• Challenges include identifying common substructures and mapping molecular transformations.

Purpose of the Study:

• To present an automated tool, alchemical-setup.py, for setting up relative solvation and binding free energy calculations.
• To integrate alchemical-setup.py with the Lead Optimization Mapper (LOMAP) for fully automated workflows.
• To simplify and accelerate the process of performing complex free energy simulations.

Main Methods:

• Developed alchemical-setup.py to automatically generate input files for GROMACS MD package.
• Integrated alchemical-setup.py with LOMAP to utilize molecular mapping and calculation graphs.
• Generated topology, coordinate files, and simulation parameters for relative free energy calculations.

Main Results:

• Successfully automated the setup of relative solvation and binding free energy calculations.
• Validated the tool by performing relative hydration free energy calculations for SAMPL4 challenge molecules.
• Achieved good agreement with previously published results, demonstrating tool efficacy.

Conclusions:

• alchemical-setup.py offers a straightforward and automated solution for setting up relative free energy calculations.
• The tool, in conjunction with LOMAP, significantly enhances the efficiency of computational drug discovery and molecular design.
• Enables wider accessibility and application of advanced free energy calculations in GROMACS.