Conditional Latent Space Molecular Scaffold Optimization for Accelerated Molecular Design (2411.01423v1)

Abstract: The rapid discovery of new chemical compounds is essential for advancing global health and developing treatments. While generative models show promise in creating novel molecules, challenges remain in ensuring the real-world applicability of these molecules and finding such molecules efficiently. To address this, we introduce Conditional Latent Space Molecular Scaffold Optimization (CLaSMO), which combines a Conditional Variational Autoencoder (CVAE) with Latent Space Bayesian Optimization (LSBO) to modify molecules strategically while maintaining similarity to the original input. Our LSBO setting improves the sample-efficiency of our optimization, and our modification approach helps us to obtain molecules with higher chances of real-world applicability. CLaSMO explores substructures of molecules in a sample-efficient manner by performing BO in the latent space of a CVAE conditioned on the atomic environment of the molecule to be optimized. Our experiments demonstrate that CLaSMO efficiently enhances target properties with minimal substructure modifications, achieving state-of-the-art results with a smaller model and dataset compared to existing methods. We also provide an open-source web application that enables chemical experts to apply CLaSMO in a Human-in-the-Loop setting.