University of Essex Lecture - Addressing the flexibility issue in protein-ligand binding

4 July 2022 13:00-14:00, Colchester, United Kingdom

Quantitative understanding of molecular recognition is crucial for basic research and for structure-based drug design. Key to this goal is the knowledge of the atomic-level structures of the complexes formed by receptors and their ligands.

Determining the structure of a protein by experimental techniques remains a quite demanding task in terms of both cost and duration of the experiments. Computational methods have become a valid complement to experiments, although inaccuracy increases with the extent of the conformational changes associated to protein-ligand binding.

To address this limitation, we recently introduced “EDES - Ensemble Docking with Enhanced-sampling of pocket Shape” a computational method based on metadynamics simulations to generate holo-like conformations of proteins by only exploiting their apo structure.

Here, we present an improved version of the original protocol enabling to handle multiple - allosteric - binding sites in extremely flexible proteins.

We applied our method to a very challenging target, namely the enzyme adenylate kinase (AK), which undergoes very large conformational changes upon ligand binding. Our protocol generated a significant fraction of structures featuring a low RMSD from the experimental geometry of the complex between AK and an inhibitor. These conformations were used in ensemble docking calculations yielding to native-like poses of substrates and inhibitors of adenylate kinase among the top-ranked ones.


Originally from Italy, Attilio V. Vargiu has a BSc (Honours) degree in Physics from the University of Cagliari (Italy), a PhD in Statistical and Biological Physics from the "International School of Advanced Studies" of Trieste (Italy), and several post-docs in Cagliari (Italy), Berkeley (USA), Bremen (Germany), and Utrecht (Netherlands).

He was appointed Assistant Professor at the Physics Department of the University of Cagliari in 2019.

How to attend

This seminar is being held in person in STEM 3.1 (STEM Centre on Square 1, Colchester campus). You can also watch via Zoom (meeting ID: 925 4561 0277)

If you have any queries about this seminar please email Dr Filippo Prischi (
University of Essex

STEM 3.1 (STEM Centre on Square 1, Colchester campus), University of Essex, School of Life Sciences , University of Essex , Wivenhoe Park , Colchester, CO4 3SQ, United Kingdom

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