Elastin-like polypeptides (ELPs) with the repeat sequence of VPGVG are widely used as a model system for investigation of lower critical solution temperature (LCST) transition behavior. In this ...paper, the effect of temperature on the structure, dynamics and association of (VPGVG)18 in aqueous solution is investigated using atomistic molecular dynamics simulations. Our simulations show that as the temperature increases the ELP backbones undergo gradual conformational changes, which are attributed to the formation of more ordered secondary structures such as β-strands. In addition, increasing temperature changes the hydrophobicity of the ELP by exposure of hydrophobic valine-side chains to the solvent and hiding of proline residues. Based on our simulations, we conclude that the transition behavior of (VPGVG)18 can be attributed to a combination of thermal disruption of the water network that surrounds the polypeptide, reduction of solvent accessible surface area of the polypeptide, and increase in its hydrophobicity. Simulations of the association of two (VPGVG)18 molecules demonstrated that the observed gradual changes in the structural properties of the single polypeptide chain are enough to cause the aggregation of polypeptides above the LCST. These results lead us to propose that the LCST phase behavior of poly(VPGVG) is a collective phenomenon that originates from the correlated gradual changes in single polypeptide structure and the abrupt change in properties of hydration water around the peptide and is a result of a competition between peptide–peptide and peptide–water interactions. This is a computational study of an important intrinsically disordered peptide system that provides an atomic-level description of structural features and interactions that are relevant in the LCST phase behavior.
The stimuli-responsive character of elastin-like polypeptides (ELP) has led to their use in a wide range of applications. The temperature-triggered aggregation, or LCST behavior, of ELPs is a complex ...and multistep phenomenon, which proposed to include the structural transitions, loss of hydrophobic hydration, expulsion of water molecules and physical association of chains. Thus, the origin and detailed mechanism of LCST in ELPs is difficult to elucidate. Here, to gain insights into structure and dynamics of coacervates, we performed all-atom molecular dynamics simulations of 27 90-mer ELPs in explicit water at 350 K. Two sequences, poly(VGPVG)18 and poly(VPGVG)18, were examined due to their experimentally observed differences in thermal hysteresis albeit identical overall composition but different arrangement of amino acids. The simulation results indicate that surface hydrophobicity of poly(VGPVG) aggregate is less than that of the poly(VPGVG) aggregate, and there are marked changes in torsion angles and the propensities of secondary structural motifs during the aggregation process. Moreover, there are significant differences between structure of a single polypeptide in water and structure within the aggregate. Overall, the aggregation process is driven by the formation of peptide–peptide interactions whereas the average hydration of peptides remains almost the same between dissolved and aggregated states. Even though the aggregation is driven by the hydrophobic interactions, ELP coacervate has no hydrophobic core and contains many water molecules. Overall, our findings provide an insight into the sequence-dependent structure of coacervates and molecular behavior of individual peptides during aggregation.
The physical origin of the lower critical solution temperature (LCST) behavior of a variety of fluids, including elastin-like polypeptides (ELPs), has been studied for the past few decades. As is the ...case for polymer solutions, LCST behavior of ELPs is invariably reported for large systems of molecules and is considered evidence for collective behavior. In contrast, we find evidence for properties changes associated with LCST behavior in a single molecule by performing long atomic-level molecular dynamics simulation on the ELP sequences (Val-Pro-Gly-Val-Gly)n for four different length peptides over a wide range of temperatures. We observe a sharp transition in the number of hydrogen bonds between peptide and water and in the number of water molecules within the first hydration shell as temperature rises; this is used to locate the transition temperature. The dependence of the transition temperatures of ELPs on their lengths agrees well with experiments in that both have the same power law exponents. Our simulations reveal that the tendency for pentamers (VPGVG) in ELPs of all lengths to lose H-bonds with water or to gain H-bonds with themselves as temperature rises is independent of the length of the chain in which they are embedded. Thus, the transition temperature of ELPs in pure water is determined by two factors: the hydrogen bonding tendency of the pentamers and the number of pentamers per ELP. Moreover, the hydrogen bonding tendency of pentamers depends only on their sequences, not on the ELP chain length.
Elastin-like polypeptides (ELP) exhibit an inverse temperature transition or lower critical solution temperature (LCST) transition phase behavior in aqueous solutions. In this paper, the thermal ...responsive properties of the canonical ELP, poly(VPGVG), and its reverse sequence poly(VGPVG) were investigated by turbidity measurements of the cloud point behavior, circular dichroism (CD) measurements, and all-atom molecular dynamics (MD) simulations to gain a molecular understanding of mechanism that controls hysteretic phase behavior. It was shown experimentally that both poly(VPGVG) and poly(VGPVG) undergo a transition from soluble to insoluble in aqueous solution upon heating above the transition temperature (T t). However, poly(VPGVG) resolubilizes upon cooling below its T t, whereas the reverse sequence, poly(VGPVG), remains aggregated despite significant undercooling below the T t. The results from MD simulations indicated that a change in sequence order results in significant differences in the dynamics of the specific residues, especially valines, which lead to extensive changes in the conformations of VPGVG and VGPVG pentamers and, consequently, dissimilar propensities for secondary structure formation and overall structure of polypeptides. These changes affected the relative hydrophilicities of polypeptides above T t, where poly(VGPVG) is more hydrophilic than poly(VPGVG) with more extended conformation and larger surface area, which led to formation of strong interchain hydrogen bonds responsible for stabilization of the aggregated phase and the observed thermal hysteresis for poly(VGPVG).
Rational design of supramolecular nanomaterials fundamentally depends upon an atomic-level understanding of their structure and how it responds to chemical modifications. Here we studied a series of ...crystalline diblock copolypeptoids by a combination of sequence-controlled synthesis, cryogenic transmission electron microscopy, and molecular dynamics simulation. This family of amphiphilic polypeptoids formed free-floating 2-dimensional monolayer nanosheets, in which individual polymer chains and their relative orientations could be directly observed. Furthermore, bromine atom side-chain substituents in nanosheets were directly visualized by cryogenic transmission electron microscopy, revealing atomic details in position space inaccessible by conventional scattering techniques. While the polypeptoid backbone conformation was conserved across the set of molecules, the nanosheets exhibited different lattice packing geometries dependent on the aromatic side chain para substitutions. Peptoids are inherently achiral, yet we showed that sequences containing an asymmetric aromatic substitution pattern pack with alternating rows adopting opposite backbone chiralities. These atomic-level insights into peptoid nanosheet crystal structure provide guidance for the future design of bioinspired nanomaterials with more precisely controlled structures and properties.
Peptoid polymers with sequence-defined side chains are observed to self-assemble into a variety of structures spanning nanometer and micron scales. We explored a diblock copolypeptoid, ...poly(N-decylglycine)10-block-poly(N-2-(2-(2-methoxyethoxy)ethoxy)-ethylglycine)10 (abbreviated as Ndc10-Nte10), which forms crystalline nanofibers and nanosheets as evidenced by recent cryo-transmission electron microscopy, atomic force microscopy, X-ray diffraction, and calorimetry. Using all-atom molecular dynamics simulations, we examined the thermodynamic forces driving such self-assembly and how nanoscale morphology is tailored through modification of the N-terminus or via the addition of small molecules (urea). We have found that the hydrophobic Ndc domain alignment is key to the formation of molecular stacks whose growth is limited by electrostatic repulsion between protonated N-termini. These stacks are the building blocks that assemble via cooperative van der Waals attraction between the tips of extended decyl side chains to form nanofibers or nanosheets with a well-converged intermolecular interaction energy. Assemblies are significantly more stable in urea solution due to its strong attraction to the peptoid–solvent interface. Isolated peptoids exhibit curved all-cis backbones, which straighten within molecular stacks to maximize contact and registry between neighboring molecules. We hypothesize that competition between this attractive interaction and a strain cost for straightening the backbone is what leads to finite stack widths that define crystalline nanofibers of protonated Ndc10-Nte10. Growth is proposed to proceed through backbone unfurling via trans defects, which is more prevalent in aqueous solution than in THF, indicating a possible pathway to self-assembly under experimentally defined synthesis conditions (viz., THF evaporation).
Crystalline nanosheets formed by amphiphilic block copolypeptoids with halogenated phenyl side chains were imaged at the atomic-scale using cryogenic transmission electron microscopy (cryo-TEM). In ...general, the polypeptoid molecules adopt V-shaped configurations in the crystalline state, and adjacent molecules can pack with one another in either parallel or antiparallel arrangements, depending on the chemical composition. The halogen bond, which can have characteristic energies ranging from 1 to 5 kcal/mol, is commensurate with the parallel configuration. However, cryo-TEM images show that chains in the halogenated crystals were in the antiparallel configuration. Molecular dynamics (MD) simulations show that positively charged σ-holes, which are characteristic of halogen atoms covalently bonded to carbon atoms, play an important role in determining crystal geometry. Parallel and antiparallel configurations exhibited similar stability in simulations when standard force fields that only account for the electronegativity of halogen atoms were used. However, including the σ-hole in the simulations resulted in a destabilization of the parallel configuration. This combination of imaging and simulation, which has played an important role in structural biology, has the potential to improve our understanding of factors that govern noncovalent interactions in synthetic materials.
The phase separation behavior of intrinsically disordered proteins (IDPs) is thought of as analogous to that of polymers that undergo equilibrium lower or upper critical solution temperature (LCST ...and UCST, respectively) phase transition. This view, however, ignores possible nonequilibrium properties of protein assemblies. Here, by studying IDP polymers (IDPPs) composed of repeat motifs that encode LCST or UCST phase behavior, we discovered that IDPs can access a wide spectrum of nonequilibrium, hysteretic phase behaviors. Experimentally and through simulations, we show that hysteresis in IDPPs is tunable and that it emerges through increasingly stable interchain interactions in the insoluble phase. To explore the utility of hysteretic IDPPs, we engineer self-assembling nanostructures with tunable stability. These findings shine light on the rich phase separation behavior of IDPs and illustrate hysteresis as a design parameter to program nonequilibrium phase behavior in self-assembling materials.
The development of nucleic acid (NA) based nanotechnology applications rely on the efficient packaging of DNA and RNA. However, the atomic details of NA–nanoparticle binding remains to be ...comprehensively characterized. Here, we examined how nanoparticle and solvent properties affect NA compaction. Our large-scale, all-atom simulations of ligand-functionalized gold nanoparticle (NP) binding to double stranded NAs as a function of NP charge and solution salt concentration reveal different responses of RNA and DNA to cationic NPs. We demonstrate that the ability of a nanoparticle to bend DNA is directly correlated with the NPs charge and ligand corona shape, where more than 50% charge neutralization and spherical shape of the NP ligand corona ensured the DNA compaction. However, NP with 100% charge neutralization is needed to bend DNA almost as efficiently as the histone octamer. For RNA in 0.1 M NaCl, even the most highly charged nanoparticles are not capable of causing bending due to charged ligand end groups binding internally to the major groove of RNA. We show that RNA compaction can only be achieved through a combination of highly charged nanoparticles with low salt concentration. Upon interactions with highly charged NPs, DNA bends through periodic variation in groove widths and depths, whereas RNA bends through expansion of the major groove.
Emulsion-based, resonant infrared matrix-assisted pulsed laser evaporation (RIR-MAPLE) has been demonstrated as an alternative technique to deposit conjugated polymer films for photovoltaic ...applications; yet, a fundamental understanding of how the emulsion target characteristics translate into film properties and solar cell performance is unclear. Such understanding is crucial to enable the rational improvement of organic solar cell (OSC) efficiency and to realize the expected advantages of emulsion-based RIR-MAPLE for OSC fabrication. In this paper, the effect of the primary solvent used in the emulsion target is studied, both experimentally and theoretically, and it is found to determine the conjugated polymer cluster size in the emulsion as well as surface roughness and internal morphology of resulting polymer films. By using a primary solvent with low solubility-in-water and low vapor pressure, the surface roughness of deposited P3HT and PCPDTBT polymer films was reduced to 10 nm, and the efficiency of P3HT:PC61BM OSCs was increased to 3.2% (∼100 times higher compared to the first MAPLE OSC demonstration Caricato A. P. ; Appl. Phys. Lett. 2012, 100, 073306 ). This work unveils the mechanism of polymer film formation using emulsion-based RIR-MAPLE and provides insight and direction to determine the best ways to take advantage of the emulsion target approach to control film properties for different applications.
PDF
