Modeling the Self-Assembly of Peptide Amphiphiles into Fibers Using Coarse-Grained Molecular Dynamics

Lee, One Sun; Cho, Vince; Schatz, George C.

doi:10.1021/nl302487m

Cited by 147 publications

(188 citation statements)

References 47 publications

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“…31,35 SSNMR experiments are an ideal complement to MARTINI since peptide secondary structure needs to be assigned at the beginning of the simulation and remains constant over the trajectory. Based on the ssNMR data, residues A2 -L7 were assigned as β-strand, similarly to W8 that links the hydrophobic and the hydrophilic peptide parts.…”

Section: Resultsmentioning

confidence: 99%

The Supramolecular Organization of a Peptide-Based Nanocarrier at High Molecular Detail

et al. 2015

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Nanovesicles self-assembled from amphiphilic peptides are promising candidates for applications in drug delivery. However, complete high-resolution data on the local and supramolecular organization of such materials has been elusive thus far, which is a substantial obstacle to their rational design. In the absence of precise information, nanovesicles built of amphiphilic "lipid-like" peptides are generally assumed to resemble liposomes that are organized from bilayers of peptides with a tail-to-tail ordering. Using the nanocarrier formed by the amphiphilic self-assembling peptide 2 (SA2 peptide) as an example, we derive the local and global organization of a multimega-Dalton peptide-based nanocarrier at high molecular detail and at close-to physiological conditions. By integrating a multitude of experimental techniques (solid-state NMR, AFM, SLS, DLS, FT-IR, CD) with large- and multiscale MD simulations, we show that SA2 nanocarriers are built of interdigitated antiparallel β-sheets, which bear little resemblance to phospholipid liposomes. Our atomic level study allows analyzing the vesicle surface structure and dynamics as well as the intermolecular forces between peptides, providing a number of potential leads to improve and tune the biophysical properties of the nanocarrier. The herein presented approach may be of general utility to investigate peptide-based nanomaterials at high-resolution and at physiological conditions.

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Section: Resultsmentioning

confidence: 99%

The Supramolecular Organization of a Peptide-Based Nanocarrier at High Molecular Detail

et al. 2015

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“…16 Therefore, if this parameter was not key for a PA formed by 13 amino acids, it can be expected to be less influential for the tetra-and hexapeptides of this study. All systems were built in a cubic box 21.5 × 21.5 × 21.5 nm 3 and solvated using CG water.…”

Section: Systemsmentioning

confidence: 87%

Molecular dynamics simulations reveal disruptive self-assembly in dynamic peptide libraries

et al. 2017

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There is significant interest in the use of unmodified self-assembling peptides as building blocks for functional, supramolecular biomaterials. Recently, dynamic peptide libraries (DPLs) have been proposed to select self-assembling materials from dynamically exchanging mixtures of dipeptide inputs in the presence of a nonspecific protease enzyme, where peptide sequences are selected and amplified based on their self-assembling tendencies. It was shown that the results of the DPL of mixed sequences (e.g. starting from a mixture of dileucine, L 2 , and diphenylalanine, F 2 ) did not give the same outcome as the separate L 2 and F 2 libraries (which give rise to the formation of F 6 and L 6 ), implying that interactions between these sequences could disrupt the self-assembly. In this study, coarse grained molecular dynamics (CG-MD) simulations are used to understand the DPL results for F 2 , L 2 and mixed libraries. CG-MD simulations demonstrate that interactions between precursors can cause the low formation yield of hexapeptides in the mixtures of dipeptides and show that this ability to disrupt is influenced by the concentration of the different species in the DPL. The disrupting self-assembly effect between the species in the DPL is an important effect to take into account in dynamic combinatorial chemistry as it affects the possible discovery of new materials. This work shows that combined computational and experimental screening can be used complementarily and in combination providing a powerful means to discover new supramolecular peptide nanostructures.

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“…FiGURe 12 | Assembly process of a nanofiber from a random configuration (Lee et al, 2012a). Reprinted with permission from American Chemical Society.…”

Section: Peptidesmentioning

confidence: 99%

“…As shown in Figure 12, spherical micelles were initially formed, then aggregated into a three-dimensional network, and finally merged into a nanofiber. Consistent with FAMD simulation, water molecules were excluded from the hydrophobic core (Lee et al, 2012a). Two peptide amphiphiles with variation in the content of valine and alanine ratios (PA1: V2A4E3 and PA2: V4A2E3) were also investigated by them.…”

Section: F4h5k15 F8h5k15 F12h5k15 F16h5k15mentioning

confidence: 99%

Computational Amphiphilic Materials for Drug Delivery

Thota

Jiang

2015

Front. Mater.

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Amphiphilic materials can assemble into a wide variety of morphologies and have emerged as a novel class of candidates for drug delivery. Along with a large number of experiments reported, computational studies have also been conducted in this field. At an atomistic/molecular level, computations can facilitate quantitative understanding of experimental observations and secure fundamental interpretation of underlying phenomena. This review summarizes the recent computational studies on amphiphilic copolymers and peptides for drug delivery. Atom-resolution and time-resolved insights are provided from bottom-up to microscopically elucidate the mechanisms of drug loading/release, which are indispensable in the rational screening and design of new amphiphiles for high-efficacy drug delivery.

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Modeling the Self-Assembly of Peptide Amphiphiles into Fibers Using Coarse-Grained Molecular Dynamics

Cited by 147 publications

References 47 publications

The Supramolecular Organization of a Peptide-Based Nanocarrier at High Molecular Detail

The Supramolecular Organization of a Peptide-Based Nanocarrier at High Molecular Detail

Molecular dynamics simulations reveal disruptive self-assembly in dynamic peptide libraries

Computational Amphiphilic Materials for Drug Delivery

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