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.

A Spatial Artificial Chemistry Implementation of a Gene Regulatory Network Aimed at Generating Protein Concentration Dynamics.

Gene regulatory networks are networks of interactions in organisms responsible for determining the production levels of proteins and peptides. Mathematical and computational models of gene regulatory networks have been proposed, some of them rather abstract and called artificial regulatory networks. In this contribution, a spatial model for gene regulatory networks is proposed that is biologically more realistic and incorporates an artificial chemistry to realize the interaction between regulatory proteins called the transcription factors and the regulatory sites of simulated genes. The result is a system that is quite robust while able to produce complex dynamics similar to what can be observed in nature. Here an analysis of the impact of the initial states of the system on the produced dynamics is performed, showing that such models are evolvable and can be directed toward producing desired protein dynamics.

Computational Peptide Discovery with a Genetic Programming Approach.

Background: 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 space. In silico methods can accelerate research and substantially reduce costs. Evolutionary algorithms are a promising approach for exploring large search spaces and facilitating the discovery of new peptides. Results: This study presents the development and use of a variant of the initial POET algorithm, called POETRegex, which is based on genetic programming, where individuals are represented by a list of regular expressions. The program was trained on a small curated dataset and employed to predict new peptides that can improve the problem of sensitivity in detecting peptides through magnetic resonance imaging using chemical exchange saturation transfer (CEST). The resulting model achieves a performance gain of 20% over the initial POET variant and is able to predict a candidate peptide with a 58% performance increase compared to the gold-standard peptide. Conclusions: By combining the power of genetic programming with the flexibility of regular expressions, new potential peptide targets were identified to 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.

A Genetic Programming Approach to Engineering MRI Reporter Genes.

Here we develop a mechanism of protein optimization using a computational approach known as "genetic programming". We developed an algorithm called Protein Optimization Engineering Tool (POET). Starting from a small library of literature values, the use of this tool allowed us to develop proteins that produce four times more MRI contrast than what was previously state-of-the-art. Interestingly, many of the peptides produced using POET were dramatically different with respect to their sequence and chemical environment than existing CEST producing peptides, and challenge prior understandings of how those peptides function. While existing algorithms for protein engineering rely on divergent evolution, POET relies on convergent evolution and consequently allows discovery of peptides with completely different sequences that perform the same function with as good or even better efficiency. Thus, this novel approach can be expanded beyond developing imaging agents and can be used widely in protein engineering.