TG-CDDPM: text-guided antimicrobial peptides generation based on conditional denoising diffusion probabilistic model.

Antimicrobial peptides (AMPs) have emerged as a promising substitution to antibiotics thanks to their boarder range of activities, less likelihood of drug resistance, and low toxicity. Traditional biochemical methods for AMP discovery are costly and inefficient. Deep generative models, including the long-short term memory model, variational autoencoder model, and generative adversarial model, have been widely introduced to expedite AMP discovery. However, these models tend to suffer from the lack of diversity in generating AMPs. The denoising diffusion probabilistic model serves as a good candidate for solving this issue. We proposed a three-stage Text-Guided Conditional Denoising Diffusion Probabilistic Model (TG-CDDPM) to generate novel and homologous AMPs. In the first two stages, contrastive learning and inferring models are crafted to create better conditions for guiding AMP generation, respectively. In the last stage, a pre-trained conditional denoising diffusion probabilistic model is leveraged to enrich the peptide knowledge and fine-tuned to learn feature representation in downstream. TG-CDDPM was compared to the state-of-the-art generative models for AMP generation, and it demonstrated competitive or better performance with the assistance of text description as supervised information. The membrane penetration capabilities of the identified candidate AMPs by TG-CDDPM were also validated through molecular weight dynamics experiments.