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

ABSTRACT

The accurate parameterization of drug‐like molecules is a fundamental prerequisite for molecular dynamics simulations in structure‐based drug design. While the AM1‐BCC charge model has served as the de facto “standard” for GAFF2 parameterization for two decades, the recently introduced ABCG2 model offers substantially improved accuracy in predicting hydration free energies and other key physicochemical properties. However, accessing ABCG2 parameters traditionally requires downloading and installing the full AmberTools suite—a multi‐gigabyte software package with complex dependencies—presenting a significant barrier for many practitioners, particularly experimental collaborators and researchers new to the field. Here we present a major upgrade to the PrimaDORAC web interface that makes ABCG2 parameterization readily accessible to the entire drug design community. Through a minimalistic integration of essential AmberTools components directly into the web application framework, users can now obtain GAFF2 parameters with ABCG2 charges for any drug‐like molecule in seconds, without any software installation. The interface accepts a single SMILES string or structure file and returns a complete archive containing GROMACS‐compatible topology files and a ready‐to‐use PDB structure. By removing all technical barriers to accessing state‐of‐the‐art ABCG2 parameters, the upgraded PrimaDORAC interface is aimed at empowering medicinal chemists, pharmacologists, and computational researchers alike to conduct more accurate MD simulations with minimal effort. The service is freely available at www1.chim.unifi.it/orac .