Extending the Python RESP Framework for Extra Point Charge Fitting

Abstract

The Restrained Electrostatic Potential (RESP) method is widely used to derive electrostatic parameters for molecular mechanics-based models. However, conventional nuclei-centered charge models can struggle to reproduce anisotropic features such as halogen σ-holes and electron lone-pair regions. Herein, an extension of the Psi4-compatible Python resp implementation of Alenaizen et al. is presented that enables partial atomic charge fitting to user-defined extra point sites represented as massless dummy particles. This reengineering introduces an INI-based configuration layer, a revised driver.py that propagates extra point sites through grid/ESP handling, an updated espfit.py engine that continues to support multiconformer fitting, and an updated extras.py that includes functions for adding extra point centers to the fitting. Also introduced are functions for computing RMSE and RRMSE metrics, along with support for the recently developed van der Waals radii by Charry and Tkatchenko. Several examples are provided that demonstrate Stage 1 and Stage 2 fitting involving a single conformation, multiple conformations, as well as the generation and use of multiple spatial orientations. The resulting workflow is transparent, reproducible, and enables the development of both nuclei- and off-centered electrostatic models for molecular mechanics-based simulations.