Fig. 3. Lead optimization using DeepLigBuilder. (a) The topological structure of MI-23, a reported covalent inhibitor targeting SARS-CoV-2 Mpro.54 The blue part of the molecule is used as a seed structure by DeepLigBuilder for molecule generation. (b) The range of the scores for the 10 best molecules sampled at each step during the Monte Carlo tree search. Blue: MCTS turned on; grey: MCTS turned off. (c) The distribution of the smina score, QED, and SAscore of high-quality samples. (d) The distribution of hydrophobic groups in high-quality samples. (e) The distribution of hydrogen bond acceptors in high-quality samples. (f–h) Examples of molecules generated by DeepLigBuilder. The binding poses of the generated molecules (grey) are aligned with MI-23 (light grey) for comparison. The residue Glu166 is shown in blue. Molecular properties and predicted binding affinities are listed in the grey boxes.
