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Updated: Dec 23, 2025

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Learning (from) the Electron Density: Transferability, Conformational and Chemical Diversity
Alberto Fabrizio1, Ksenia Briling1, Andrea Grisafi2
1Laboratory for Computational Molecular Design, Institut des Sciences et Ingénierie Chimiques, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Abstract:
Machine-learning in quantum chemistry is currently booming, with reported applications spanning all molecular properties from simple atomization energies to complex mathematical objects such as the many-body wavefunction. Due to its central role in density functional theory, the electron density is a particularly compelling target for non-linear regression. Nevertheless, the scalability and the transferability of the existing machine-learning models of ρ(r) are limited by its complex rotational symmetries. Recently, in collaboration with Ceriotti and coworkers, we combined an efficient electron density decomposition scheme with a local regression framework based on symmetry-adapted Gaussian process regression able to accurately describe the covariance of the electron density spherical tensor components. The learning exercise is performed on local environments, allowing high transferability and linear-scaling of the prediction with respect to the number of atoms. Here, we review the main characteristics of the model and show its predictive power in a series of applications. The scalability and transferability of the trained model are demonstrated through the prediction of the electron density of Ubiquitin.
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