One of the main challenges in small molecule drug discovery is finding novel chemical compounds with desirable properties. In this work, we propose a novel method that combines in silico prediction of molecular properties such as biological activity or pharmacokinetics with an in silico optimization algorithm, namely Particle Swarm Optimization. Our method takes a starting compound as input and proposes new molecules with more desirable (predicted) properties. It navigates a machine-learned continuous representation of a drug-like chemical space guided by a defined objective function. The objective function combines multiple in silico prediction models, defined desirability ranges and substructure constraints. We demonstrate that our proposed method is able to consistently find more desirable molecules for the studied tasks in relatively short time. We hope that our method can support medicinal chemists in accelerating and improving the lead optimization process.
