Secondary structure determines electron transport in peptides

Abstract

AbstractProteins play a key role in biological electron transport, but the structure-function relationships governing the electronic properties of peptides are not fully understood. Despite recent progress, understanding the link between peptide conformational flexibility, hierarchical structures, and electron transport pathways has been challenging. Here, we use single-molecule experiments, molecular dynamics (MD) simulations, non-equilibrium Green’s function-density functional theory (NEGF-DFT) calculations, and unsupervised machine learning to understand the role of primary amino acid sequence and secondary structure on charge transport in peptides. Our results reveal a two-state molecular conductance behavior for peptides across several different amino acid sequences. MD simulations and Gaussian mixture modeling are used to show that this two-state molecular conductance behavior arises due to the conformational flexibility of peptide backbones, with a high-conductance state arising due to a more defined secondary structure (beta turn) and a low-conductance state occurring for extended peptide structures. Conformer selection for the peptide structures is rationalized using principal component analysis (PCA) of intramolecular hydrogen bonding distances along peptide backbones. Molecular conformations from MD simulations are used to model charge transport in NEGF-DFT calculations, and the results are in reasonably good agreement with experiments. Projected density of states (PDOS) calculations and molecular orbital visualizations are further used to understand the role of amino acid side chains on transport. Overall, our results show that secondary structure plays a key role in electron transport in peptides, which provides new avenues for understanding the electronic properties of longer peptides or proteins.Significance StatementElectron transport in proteins serves as a biological power line that fuels cellular activities such as respiration and photosynthesis. Within cells, proteins act as conduits, shuttling electrons through a series of reactions and pathways to generate proton gradients and to fuel ATP synthesis. Despite recent progress, the mechanisms underlying the flow of energy in protein complexes are not fully understood. Here, we study electron transport in peptides at the single-molecule level by combining experiments and molecular modeling. Our results reveal two distinct molecular sub-populations underlying electron transport that arise due to the flexibility of peptide backbones and the ability to fold into compact structures. This work provides a basis for understanding energy flow in larger proteins or biomolecular assemblies.