Recorded 3/3/2026

Speaker: Dr. Filipe Menezes (Helmholtz Institute)

Chair: Dr. Jennifer Fleming (EMBL-EBI)

Abstract:
Understanding interactions in biomacromolecular structures is challenging, particularly when detailed chemical analyses are required in a structural context, such as the presence of ligands, cofactors, or ions. We present In-Pocket Analysis (IPA), a computational tool designed to support the three-dimensional chemical interpretation of biomolecular interfaces by analysing ligand chemistry within binding-pocket geometries.
IPA addresses the gap between geometric refinement and chemically plausible local environments. By sampling and optimising experimentally compatible tautomeric, protonation, and conformational states, IPA supports validation of protein-ligand interfaces and enables a chemically consistent interpretation of local structural environments. Tests on diverse macromolecular structures suggest that IPA can highlight chemical features that are sometimes underrepresented or overlooked in deposited structural models. By complementing conventional refinement approaches, IPA offers structural biologists and modellers a practical tool for structural model building and completion, with additional potential applications in structure-based drug discovery and machine learning.

Link to preprint: https://www.biorxiv.org/content/10.1101/2025.09.24.678379v4