Computational peptide discovery with a genetic programming approach

The development of peptides for therapeutic targets or biomarkers for disease diagnosis is a challenging task in protein engineering. Current approaches are tedious, often time-consuming and require complex laboratory data due to the vast search spaces that need to be considered. In silico methods can accelerate research and substantially reduce costs. Evolutionary algorithms are a promising approach for exploring large search spaces and can facilitate the discovery of new peptides. This study presents the development and use of a new variant of the genetic-programming-based POET algorithm, called POET_Regex, where individuals are represented by a list of regular expressions. This algorithm was trained on a small curated dataset and employed to generate new peptides improving the sensitivity of peptides in magnetic resonance imaging with chemical exchange saturation transfer (CEST). The resulting model achieves a performance gain of 20% over the initial POET models and is able to predict a candidate peptide with a 58% performance increase compared to the gold-standard peptide. By combining the power of genetic programming with the flexibility of regular expressions, new peptide targets were identified that improve the sensitivity of detection by CEST. This approach provides a promising research direction for the efficient identification of peptides with therapeutic or diagnostic potential.