Accelerating the discovery of anticancer peptides targeting lung and breast cancers with the Wasserstein autoencoder model and PSO algorithm.

In the development of targeted drugs, anticancer peptides (ACPs) have attracted great attention because of their high selectivity, low toxicity and minimal non-specificity. In this work, we report a framework of ACPs generation, which combines Wasserstein autoencoder (WAE) generative model and Particle Swarm Optimization (PSO) forward search algorithm guided by attribute predictive model to generate ACPs with desired properties. It is well known that generative models based on Variational AutoEncoder (VAE) and Generative Adversarial Networks (GAN) are difficult to be used for de novo design due to the problems of posterior collapse and difficult convergence of training. Our WAE-based generative model trains more successfully (lower perplexity and reconstruction loss) than both VAE and GAN-based generative models, and the semantic connections in the latent space of WAE accelerate the process of forward controlled generation of PSO, while VAE fails to capture this feature. Finally, we validated our pipeline on breast cancer targets (HIF-1) and lung cancer targets (VEGR, ErbB2), respectively. By peptide-protein docking, we found candidate compounds with the same binding sites as the peptides carried in the crystal structure but with higher binding affinity and novel structures, which may be potent antagonists that interfere with these target-mediated signaling.