Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

Abstract

Synthetic oligopeptides containing π -conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterise an implicit solvent model to simulate early-stage self-assembly. Under low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of F ≈ −25k B T . Aggregation at high-pH produces disordered aggregates destabilised by Coulombic repulsion between negatively charged Asp termini ( F ≈ −5k B T ). In simulations of hundreds of monomers over 70 ns we observe the spontaneous formation of up to undecameric aggregates under low-pH conditions. Modeling assembly as a continuoustime Markov process, we infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide sequence and aromatic core chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates. ARTICLE HISTORY

Peptide framework for screening the effects of amino acids on assembly

“…For example, Amirkulova et al ( 31 ) relied on biasing methods to induce a small four-peptide system to aggregate into structures consistent with experimental nuclear magnetic resonance measurements. Thurston et al ( 32 ) used Markov state models from all-atom simulations to model the self-assembly of a larger peptide system. Guo et al ( 33 ) used enhanced sampling methods to understand the dimerization process that nucleates fibrillization in Aβ.…”

Discovery of Self-Assembling π-Conjugated Peptides by Active Learning-Directed Coarse-Grained Molecular Simulation

“…27 The DXXX-OPV3-XXXD family has attracted considerable experimental and computational attention in recent years due to their demonstrated capability to assemble into pseudo-1D optically and electronically active nanoaggregates whose structure and properties can be tuned through selection of the X residues. 17,22,25,[28][29][30] Assembly in aqueous solvent under acidic conditions is driven by hydrophobic, π-π stacking, and hydrogen bonding interactions. 25,27,28,31 The assembly of elongated peptides into linear aggregates with in-register stacking and alignment of the π-cores favors π orbital overlap, electronic delocalization along the backbone of the nanoaggragate, and the emergence of optical and electronic functionality such as well-defined absorption and emission spectra, HOMO/LUMO gaps, electron/hole conductivity, and exciton splitting capabilities (Fig.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12] These peptidic materials have proven readily synthesizable and responsive to external control mediated by pH, flow, light, salt concentration, and temperature, [13][14][15][16][17][18][19][20] and have found a host of potential applications in the context of photovoltaic power generation, energy harvesting, and as organic transistors. 7,9,[21][22][23][24][25][26][27] The structural and functional properties of the self-assembled nanoaggregates are governed by the molecular chemistry of the π-core and the amino acid sequence of the peptide wings.…”

“…17,22,25,[28][29][30] Assembly in aqueous solvent under acidic conditions is driven by hydrophobic, π-π stacking, and hydrogen bonding interactions. 25,27,28,31 The assembly of elongated peptides into linear aggregates with in-register stacking and alignment of the π-cores favors π orbital overlap, electronic delocalization along the backbone of the nanoaggragate, and the emergence of optical and electronic functionality such as well-defined absorption and emission spectra, HOMO/LUMO gaps, electron/hole conductivity, and exciton splitting capabilities (Fig. 1b,c).…”

Multicomponent peptide assemblies

“…While the same noncovalent interactions govern the formation of single component self-assembled peptide nanostructures and multicomponent coassembled nanostructures, 99–102 the kinetic and thermodynamic parameters that influence these processes are of special interest in the controlled coassembly of multicomponent materials. 102,103 Environmental factors such as temperature, 104,105 pH, 104–106 salt effects, 107–109 and solvent interactions 110–115 have been shown to influence the kinetics and thermodynamics peptide self-assembly in ways that dictate the ultimate supramolecular materials that are formed. When considering coassembly of multiple peptides, the kinetics and thermodynamics of both self-assembly and coassembly of the various components must be accounted for in order to selectively form the desired multicomponent materials.…”