Automatic generation of functional peptides with desired bioactivity and membrane permeability using Bayesian optimization

Abstract Peptides are potentially useful modalities of drugs; however, cell membrane permeability is an obstacle in peptide drug discovery. The identification of bioactive peptides for a therapeutic target is also challenging because of the huge amino acid sequence patterns of peptides. In this study, we propose a novel computational method, PEptide generation system using Neural network Trained on Amino acid sequence data and Gaussian process‐based optimizatiON (PENTAGON), to automatically generate new peptides with desired bioactivity and cell membrane permeability. In the algorithm, we mapped peptide amino acid sequences onto the latent space constructed using a variational autoencoder and searched for peptides with desired bioactivity and cell membrane permeability using Bayesian optimization. We used our proposed method to generate peptides with cell membrane permeability and bioactivity for each of the nine therapeutic targets, such as the estrogen receptor (ER). Our proposed method outperformed a previously developed peptide generator in terms of similarity to known active peptide sequences and the length of generated peptide sequences.