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PhD Defence

To explore the drug space smarter: Artificial intelligence in drug design for G protein-coupled receptors

  • X. Liu
Tuesday 15 February 2022
Academy Building
Rapenburg 73
2311 GJ Leiden


  • Prof. A.P. IJzerman
  • Prof. G.J.P. van Westen
  • Prof. Kai Ye (Xi'An Jiaotong University)


Over several decades, a variety of computational methods for drug discovery have been proposed and applied in practice. With the accumulation of data and the development of machine learning methods, computational drug design methods have gradually shifted to a new paradigm, i.e. deep learning methods have attracted particular interest in drug design.

In this study, a new deep learning-based method (DrugEx) was proposed to design de novo drug-like molecules. It was proven that candidate molecules designed by DrugEx had a larger chemical diversity, and better covered the chemical space of known ligands. In order to address the issue of polypharmacology, the DrugEx algorithm was updated with multi-objective optimization towards multiple targets. The results of its application demonstrated the generation of compounds with a diverse predicted selectivity profile toward multiple targets, offering the potential of high efficacy and lower toxicity.

In order to improve its generality, DrugEx was further updated to have the capability of designing molecules based on given scaffolds. We extended the architecture of Transformer to deal with each molecule as a graph. As a proof, its effectiveness in that 100% valid molecules are generated and most of them had predicted high affinity towards A2AAR with given scaffolds.

Moreover, GenUI was developed as a visualizion software platform that makes it possible to integrate molecular generators within a feature-rich graphical user interface to facilitate collaboration in the disparate communities interested in computer-aided drug discovery.

These studies highlight the overwhelming power of AI methods in drug discovery.

PhD dissertations

PhD dissertations by Leiden PhD students are available digitally after the defence through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.

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