(147a) Amino Acid Sequence Controls Electron Transport in Peptides and Heme-Binding Peptide Monolayers

Proteins play a key role in biological electron transport, but the structure-function relationships governing the electronic properties of peptides are not fully understood. In this talk, I will discuss the role of amino acid sequence on electron transport in peptides using a combination of single-molecule experiments, molecular dynamics (MD) simulations, and quantum transport calculations. In recent work, we observed an unexpected two-state molecular conductance behavior for peptides across several different amino acid sequences. A high-conductance state arises due to a defined secondary structure (beta turn or 3-10 helices), and a low-conductance state arises for extended peptide structures. These results highlight the importance of intramolecular H-bonding and helical conformations on electron transport in peptides. Active learning is combined with experiments, theory, and simulations to understand and predict the electronic properties of large libraries of peptides with different amino acid sequences, including 324 tetrapeptides and 5832 pentapeptides. Using this approach, we demonstrate the ability to predict the electronic properties of folded molecular structures across a broad range of amino acid sequences. In a second project, the electronic properties of a series of heme-binding peptides based on cytochrome bc1 are studied using molecular electronics experiments and simulations. Self-assembled monolayers (SAMs) are prepared using sequence-defined heme-binding peptides capable of forming helical secondary structures. Following monolayer formation, the structural properties and chemical composition of assembled peptides are determined using atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS), and the electronic properties (I-V curves) are characterized using a soft contact liquid metal electrode method based on eutectic gallium-indium alloys (EGaIn). Our results show a striking 1000-fold increase in current density across SAM junctions upon addition of heme compared to identical peptide sequences in the absence of heme, while maintaining a constant junction thickness. These findings show that amino acid sequence directly controls enhancements in electron transport in heme-binding peptides. Overall, this work highlights the role of amino acid sequence in determining the electronic properties of synthetic peptides inspired by nature, providing new avenues for the design of functional bioelectronic materials.