Molecular Optimization refers to the process of systematically modifying the structure of a molecule to achieve specific desired properties or outcomes. This process is commonly employed in the fields of chemistry, biochemistry, drug discovery, and materials science. The objective is to enhance certain characteristics or functions of a molecule, making it more suitable for a particular application.

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A Deep Generative Model for Molecule Optimization via One Fragment Modification

A Deep Generative Model for Molecule Optimization via One Fragment Modification Molecule optimization is a critical step in drug development to improve the desired properties of drug candidates through chemical modification. We have developed a novel deep generative model, Modof, over molecular graphs for molecule optimization. Modof modifies a given molecule through the prediction of a single site of disconnection at the molecule and the removal and/or addition of fragments at that site. A pipeline of multiple, identical Modof models is implemented into Modof-pipe to modify an input molecule at multiple disconnection sites. Here we show that Modof-pipe is able to retain major molecular scaffolds, allow controls over intermediate optimization steps and better constrain molecule similarities. Modof-pipe outperforms the state-of-the-art methods on benchmark datasets. Without molecular similarity constraints, Modof-pipe achieves 81.2% improvement in the octanol–water partition coefficient, penalized by synthetic accessibility and ring size, and 51.2%, 25.6% and 9.2% improvement if the optimized molecules are at least 0.2, 0.4 and 0.6 similar to those before optimization, respectively. Modof-pipe is further enhanced into Modof-pipem to allow modification of one molecule to multiple optimized ones. Modof-pipem achieves additional performance improvement, at least 17.8% better than Modof-pipe.