Mos-Gen: A Generative Molecular Framework for Mosquito Insecticide Design
TL;DR
Experimental results fully validated the high-precision screening capability of the Mos-Gen framework, a motif-aware generative collaborative framework that couples the pretrained molecular representation model Uni-Mol with a variational autoencoder (VAE) specifically tailored for the design of disulfide-containing allicin derivatives as mosquito insecticides.
Abstract
Mosquito-borne infectious diseases cause more than 700000 deaths worldwide each year. The long-term use of conventional chemical insecticides has induced serious resistance problems, creating an urgent need to develop novel, highly effective, and ecologically sustainable alternatives. While existing artificial intelligence approaches in this domain have focused primarily on activity prediction and classification, they leave a critical gap in the de~novo generation of novel molecular scaffolds. In this study, we propose Mos-Gen, a motif-aware generative collaborative framework that couples the pretrained molecular representation model Uni-Mol with a variational autoencoder (VAE), specifically tailored for the design of disulfide-containing allicin derivatives as mosquito insecticides. Among the generated candidates, fourteen compounds -- comprising nine predicted positives and five predicted negatives -- were selected for chemical synthesis and experimental validation. The hit rate among the predicted positives reached 78%, whereas none of the predicted negatives exhibited mosquitocidal activity. These experimental results fully validated the high-precision screening capability of the Mos-Gen framework.