Diffusion-ACP39: A Decoder-Adaptive Latent Diffusion Framework for Generative Anticancer Peptide Discovery

Abstract Cancer remains a major global health threat, with its incidence and mortality rates consistently rising in recent years. Anticancer peptides (ACPs) are short amino acid chains that can inhibit the growth or spread of cancer cells. Compared to traditional treatments, ACPs are a promising class of potential cancer therapies due to their multiple mechanisms, potential for combination cancer therapy, enhanced immune function, lower toxicity to normal tissues, fewer side effects, and less drug resistance. Although it is necessary to explore novel ACPs, traditional wet-lab methods for selecting them are labor-intensive, time-consuming, and expensive. To accelerate the discovery of novel ACPs, we proposed Diffusion-ACP39, a latent diffusion-based generative model with synchronized seed autoencoder for anticancer peptide design, capable of generating novel peptides with lengths ranging from 5 to 39 amino acids. Furthermore, we developed RF-ACP39, a random forest classifier model to assess the generative power of Diffusion-ACP39. Finally, Diffusion-ACP39 achieved an accuracy of 94.5% when generating 10,000 peptides with RF-ACP39. We also qualitatively analyzed the differences among true ACPs, random sequences, random peptides, and generated ACPs, demonstrating that the generated ACPs are most similar to true ACPs. Competing Interest Statement The authors have declared no competing interest.