PrimaDORAC: An improved Web Interface for Rapid GAFF2 Parameter Assignment with ABCG2 Charge Models for Drug Design...

Area of Science:

• Computational chemistry
• Drug design
• Molecular modeling

Background:

• Accurate molecular parameterization is crucial for molecular dynamics (MD) simulations in structure-based drug design.
• The AM1-BCC charge model has been the standard for GAFF2 parameterization for 20 years.
• The newer ABCG2 model provides enhanced accuracy for hydration free energies and physicochemical properties.

Purpose of the Study:

• To upgrade the PrimaDORAC web interface for simplified access to ABCG2 parameters.
• To remove technical barriers associated with installing the AmberTools suite for ABCG2 parameterization.
• To make state-of-the-art molecular parameterization accessible to the broader drug design community.

Main Methods:

• Minimalistic integration of essential AmberTools components into the PrimaDORAC web application.
• Users submit a SMILES string or structure file.
• The interface processes the input and returns GROMACS-compatible topology files and a PDB structure.

Main Results:

• The upgraded PrimaDORAC interface provides rapid (seconds) GAFF2 parameterization with ABCG2 charges.
• No software installation is required, significantly lowering the barrier to entry.
• Users receive a complete archive with GROMACS-compatible files and a PDB structure.

Conclusions:

• The PrimaDORAC interface democratizes access to accurate ABCG2 parameters for MD simulations.
• Medicinal chemists, pharmacologists, and computational researchers can now perform more precise simulations with ease.
• This advancement facilitates more efficient and accurate structure-based drug design.