Self-assembling Peptide Discovery: Overcoming Human Bias With Machine Learning

Peptide materials have a wide array of functions from tissue engineering, surface coatings to catalysis and sensing. This class of biopolymer is composed of a sequence, comprised of 20 naturally occurring amino acids whose arrangement dictate the peptide functionality. While it is highly desirable to tailor the amino acid sequence, a small increase in their sequence length leads to dramatic increase in the possible candidates (e.g., from tripeptide = 20^3 or 8,000 peptides to a pentapeptide = 20^5 or 3.2 M). Traditionally, peptide design is guided by the use of structural propensity tables, hydrophobicity scales, or other desired properties and typically yields <10 peptides per study, barely scraping the surface of the search space. These approaches, driven by human expertise and intuition, are not easily scalable and are riddled with human bias. Here, we introduce a machine learning workflow that combines Monte Carlo tree search and random forest, with molecular dynamics simulations to develop a fully autonomous computational search engine (named, AI-expert) to discover peptide sequences with high potential for self-assembly (as a representative target functionality). We demonstrate the efficacy of the AI-expert to efficiently search large spaces of tripeptides and pentapeptides. Subsequent experiments on the proposed peptide sequences are performed to compare the predictability of the AI-expert with those of human experts. The AI performs on-par or better than human experts and suggests several non-intuitive sequences with high self-assembly propensity, outlining its potential to overcome human bias and accelerate peptide discovery.