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Structure-Based De Novo Molecular Generator Combined with Artificial Intelligence and Docking Simulations

submitted on 05.04.2021, 16:15 and posted on 06.04.2021, 11:08 by Biao Ma, Kei Terayama, Shigeyuki Matsumoto, Yuta Isaka, Yoko Sasakura, Hiroaki Iwata, Mitsugu Araki, Yasushi Okuno
Recently, molecular generation models based on deep learning have attracted significant attention in drug discovery. However, most existing molecular generation models have a serious limitation in the context of drug design wherein they do not sufficiently consider the effect of the three-dimensional (3D) structure of the target protein in the generation process. In this study, we developed a new deep learning-based molecular generator, SBMolGen, that integrates a recurrent neural network, a Monte Carlo tree search, and docking simulations. The results of an evaluation using four target proteins (two kinases and two G protein-coupled receptors) showed that the generated molecules had a better binding affinity score (docking score) than the known active compounds, and they possessed a broader chemical space distribution. SBMolGen not only generates novel binding active molecules but also presents 3D docking poses with target proteins, which will be useful in subsequent drug design.


Email Address of Submitting Author


RIKEN Center for Computational Science



ORCID For Submitting Author


Declaration of Conflict of Interest

There is no conflict of interest.

Version Notes

version 01