BioExcel CoE will host a webinar on Accounting for Protein and Ligand Flexibility in Molecular Docking and Virtual Screening of Challenging Targets on 28 January 2025.
Understanding the atomic-level structures of ligand-protein complexes is essential for both fundamental research and structure-based drug design. While computational methods can effectively complement experimental approaches, the accuracy of predictions tends to diminish with significant structural changes that occur during binding. Additionally, accurately describing ligand flexibility is crucial, especially in virtual screening (VS), where initial structures are often generated without considering the necessary structural adaptations that occur upon binding.
To tackle this issue related to proteins, a new computational method called gEDES (Generalized Ensemble Docking with Enhanced Sampling of Pocket Shape) has been introduced. This approach is based on metadynamics and aims to generate bound-like conformations of proteins using only their unbound structures. The upcoming webinar will present the gEDES protocol, along with SHAPER, an algorithm designed to create ligand structures that fit snugly into the binding pockets of generic receptors while adapting to their geometry.
Preliminary results will show that the dynamic shape-matching algorithm enhances the accuracy of VS campaigns in comparison to flexible docking calculations.
