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Co-assembling peptides can be crafted into supramolecular biomaterials for use in biotechnological applications, such as cell culture scaffolds, drug delivery, biosensors, and tissue engineering. Peptide co-assembly refers to the spontaneous organization of two different peptides into a supramolecular architecture. Here we use molecular dynamics simulations to quantify the effect of anionic amino acid type on co-assembly dynamics and nanofiber structure in binary CATCH(+/-) peptide systems. CATCH peptide sequences follow a general pattern: CQCFCFCFCQC, where all C's are either a positively charged or a negatively charged amino acid. Specifically, we investigate the effect of substituting aspartic acid residues for the glutamic acid residues in the established CATCH(6E-) molecule, while keeping CATCH(6K+) unchanged. Our results show that structures consisting of CATCH(6K+) and CATCH(6D-) form flatter ß-sheets, have stronger interactions between charged residues on opposing ß-sheet faces, and have slower co-assembly kinetics than structures consisting of CATCH(6K+) and CATCH(6E-). Knowledge of the effect of sidechain type on assembly dynamics and fibrillar structure can help guide the development of advanced biomaterials and grant insight into sequence-to-structure relationships.
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Nanofibras , Nanofibras/química , Simulación de Dinámica Molecular , Aminoácidos , Péptidos/química , Materiales BiocompatiblesRESUMEN
Colloidal particles with anisotropic shapes and interactions display rich phase behavior and have potential as structural bases for materials with controllable properties. In this paper, we explore the self-assembling characteristics of a new class of particles that have been shown experimentally to form reconfigurable structures: microscopic cube-shaped colloids with a magnetic dipole that is transversely offset from the particle's center of mass. We have performed in silico simulations of the dynamics of large numbers of dipolar squares in two-dimensions using discontinuous molecular dynamics (DMD). We use a coarse-grain method where the dipolar microcubes are represented by a group of four hard circles bonded together to create a rigid square in two-dimensions and two opposite charges are embedded within the square to represent a magnetic dipole. Annealing, or "slow-cooling", simulations are conducted to determine the equilibrium structures. Systems of dipolar squares tend to assemble into one of two different types of conformations: either single- or double-stranded assemblies, each with unique structures and phase diagrams in the temperature-density plane. Single-stranded assemblies form highly interconnected percolated, or gel-like, networks. In contrast, double stranded assemblies tend to form globally-aligned nematic states at high densities, although this is not seen consistently in all runs. The phase behavior of systems of dipolar squares depends not only on the system's temperature and density, but also on the type of dipole embedded within the square and on the relative number of squares with an opposite "handedness" that are present within the system.
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Peptide self-assembly, wherein molecule A associates with other A molecules to form fibrillar ß-sheet structures, is common in nature and widely used to fabricate synthetic biomaterials. Selective coassembly of peptide pairs A and B with complementary partial charges is gaining interest due to its potential for expanding the form and function of biomaterials that can be realized. It has been hypothesized that charge-complementary peptides organize into alternating ABAB-type arrangements within assembled ß-sheets, but no direct molecular-level evidence exists to support this interpretation. We report a computational and experimental approach to characterize molecular-level organization of the established peptide pair, CATCH. Discontinuous molecular dynamics simulations predict that CATCH(+) and CATCH(-) peptides coassemble but do not self-assemble. Two-layer ß-sheet amyloid structures predominate, but off-pathway ß-barrel oligomers are also predicted. At low concentration, transmission electron microscopy and dynamic light scattering identified nonfibrillar â¼20-nm oligomers, while at high concentrations elongated fibers predominated. Thioflavin T fluorimetry estimates rapid and near-stoichiometric coassembly of CATCH(+) and CATCH(-) at concentrations ≥100 µM. Natural abundance 13C NMR and isotope-edited Fourier transform infrared spectroscopy indicate that CATCH(+) and CATCH(-) coassemble into two-component nanofibers instead of self-sorting. However, 13C-13C dipolar recoupling solid-state NMR measurements also identify nonnegligible AA and BB interactions among a majority of AB pairs. Collectively, these results demonstrate that strictly alternating arrangements of ß-strands predominate in coassembled CATCH structures, but deviations from perfect alternation occur. Off-pathway ß-barrel oligomers are also suggested to occur in coassembled ß-strand peptide systems.
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Amiloide/química , Nanofibras/química , Simulación por Computador , Polimerizacion , Conformación Proteica en Lámina beta , Multimerización de Proteína , Electricidad EstáticaRESUMEN
Self-assembly of proteinaceous biomolecules into functional materials with ordered structures that span length scales is common in nature yet remains a challenge with designer peptides under ambient conditions. This report demonstrates how charged side-chain chemistry affects the hierarchical co-assembly of a family of charge-complementary ß-sheet-forming peptide pairs known as CATCH(X+/Y-) at physiologic pH and ionic strength in water. In a concentration-dependent manner, the CATCH(6K+) (Ac-KQKFKFKFKQK-Am) and CATCH(6D-) (Ac-DQDFDFDFDQD-Am) pair formed either ß-sheet-rich microspheres or ß-sheet-rich gels with a micron-scale plate-like morphology, which were not observed with other CATCH(X+/Y-) pairs. This hierarchical order was disrupted by replacing D with E, which increased fibril twisting. Replacing K with R, or mutating the N- and C-terminal amino acids in CATCH(6K+) and CATCH(6D-) to Qs, increased observed co-assembly kinetics, which also disrupted hierarchical order. Due to the ambient assembly conditions, active CATCH(6K+)-green fluorescent protein fusions could be incorporated into the ß-sheet plates and microspheres formed by the CATCH(6K+/6D-) pair, demonstrating the potential to endow functionality.
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Péptidos , Conformación Proteica en Lámina beta , Péptidos/química , GelesRESUMEN
The aggregation of monomeric amyloid ß protein (Aß) peptide into oligomers and amyloid fibrils in the mammalian brain is associated with Alzheimer's disease. Insight into the thermodynamic stability of the Aß peptide in different polymeric states is fundamental to defining and predicting the aggregation process. Experimental determination of Aß thermodynamic behavior is challenging due to the transient nature of Aß oligomers and the low peptide solubility. Furthermore, quantitative calculation of a thermodynamic phase diagram for a specific peptide requires extremely long computational times. Here, using a coarse-grained protein model, molecular dynamics (MD) simulations are performed to determine an equilibrium concentration and temperature phase diagram for the amyloidogenic peptide fragment Aß16-22 Our results reveal that the only thermodynamically stable phases are the solution phase and the macroscopic fibrillar phase, and that there also exists a hierarchy of metastable phases. The boundary line between the solution phase and fibril phase is found by calculating the temperature-dependent solubility of a macroscopic Aß16-22 fibril consisting of an infinite number of ß-sheet layers. This in silico determination of an equilibrium (solubility) phase diagram for a real amyloid-forming peptide, Aß16-22, over the temperature range of 277-330 K agrees well with fibrillation experiments and transmission electron microscopy (TEM) measurements of the fibril morphologies formed. This in silico approach of predicting peptide solubility is also potentially useful for optimizing biopharmaceutical production and manufacturing nanofiber scaffolds for tissue engineering.
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Péptidos beta-Amiloides/química , Termodinámica , Amiloide/química , Amiloide/metabolismo , Amiloide/ultraestructura , Péptidos beta-Amiloides/metabolismo , Fragmentos de Péptidos , Agregado de Proteínas , Unión Proteica , Conformación Proteica , Multimerización de Proteína , SolubilidadRESUMEN
Biological membranes are shaped by various proteins that either generate inward or outward membrane curvature. In this article, we investigate the membrane morphologies induced by mixtures of arc-shaped particles with coarse-grained modeling and simulations. The particles bind to the membranes either with their inward, concave side or their outward, convex side and, thus, generate membrane curvature of opposite sign. We find that small fractions of convex-binding particles can stabilize three-way junctions of membrane tubules, as suggested for the protein lunapark in the endoplasmic reticulum of cells. For comparable fractions of concave-binding and convex-binding particles, we observe lines of particles of the same type, and diverse membrane morphologies with grooves and bulges induced by these particle lines. The alignment and segregation of the particles is driven by indirect, membrane-mediated interactions.
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Retículo Endoplásmico , Membrana Celular , MembranasRESUMEN
Water + elastin-like polypeptides (ELPs) exhibit a transition temperature below which the chains transform from collapsed to expanded states, reminiscent of the cold denaturation of proteins. This conformational change coincides with liquid-liquid phase separation. A statistical-thermodynamics theory is used to model the fluid-phase behavior of ELPs in aqueous solution and to extrapolate the behavior at ambient conditions over a range of pressures. At low pressures, closed-loop liquid-liquid equilibrium phase behavior is found, which is consistent with that of other hydrogen-bonding solvent + polymer mixtures. At pressures evocative of deep-sea conditions, liquid-liquid immiscibility bounded by two lower critical solution temperatures (LCSTs) is predicted. As pressure is increased further, the system exhibits two separate regions of closed-loop of liquid-liquid equilibrium (LLE). The observation of bimodal LCSTs and two re-entrant LLE regions herald a new type of binary global phase diagram: Type XII. At high-ELP concentrations the predicted phase diagram resembles a protein pressure denaturation diagram; possible "molten-globule"-like states are observed at low concentration.
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Elastina/química , Péptidos/química , Simulación por Computador , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Transición de Fase , Solventes/química , Termodinámica , Temperatura de TransiciónRESUMEN
Adhesives that can stick to multiple surface types in underwater and high moisture conditions are critical for various applications such as marine coatings, sealants, and medical devices. The analysis of natural underwater adhesives shows that L-3,4-dihydroxyphenylalanine (DOPA) and functional amyloid nanostructures are key components that contribute to the adhesive powers of these natural glues. The combination of DOPA and amyloid-forming peptides into DOPA-amyloid(-forming peptide) conjugates provides a new approach to design generic underwater adhesives. However, it remains unclear how the DOPA monomers may interact with amyloid-forming peptides and how these interactions may influence the adhesive ability of the conjugates. In this paper, we investigate the behavior of DOPA monomers, (glycine-DOPA)3 chains, and a KLVFFAE and DOPA-glycine chain conjugate in aqueous environments using molecular simulations. The DOPA monomers do not aggregate significantly at concentrations lower than 1.0M. Simulations of (glycine-DOPA)3 chains in water were done to examine the intra-molecular interactions of the chain, wherein we found that there were unlikely to be interactions detrimental to the adhesion process. After combining the alternating DOPA-glycine chain with the amyloid-forming peptide KLVFFAE into a single chain conjugate, we then simulated the conjugate in water and saw the possibility of both intra-chain folding and no chain folding in the conjugate.
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Directing the assembly of colloidal particles through the use of external electric or magnetic fields shows promise for the creation of reconfigurable materials. Self-propelled particles can also be used to dynamically drive colloidal systems to nonequilibrium steady states. We investigate colloidal systems that combine both of these methods of directed assembly, simulating mixtures of passive dipolar colloids and active soft spheres in an external magnetic field using Brownian dynamics in two dimensions. In these systems, the dipolar particles align in the direction of the external field, but the active particles are unaffected by the field. The phase behaviors exhibited included a percolated dipolar network, dipolar string-fluid, isotropic fluid, and phase-separated state. We find that the external field allows the dipolar particles to form a percolated network more easily compared to when no external field is present. Additionally, the mixture phase separates at lower active particle velocity in an external field than when no field is present. Our results suggest that combining multiple methods of directing colloidal assembly could lead to new pathways to fabricate reconfigurable materials.
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Correction for 'Dynamical self-assembly of dipolar active Brownian particles in two dimensions' by Guo-Jun Liao et al., Soft Matter, 2020, 16, 2208-2223, DOI: .
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Based on Brownian Dynamics (BD) simulations, we study the dynamical self-assembly of active Brownian particles with dipole-dipole interactions, stemming from a permanent point dipole at the particle center. The propulsion direction of each particle is chosen to be parallel to its dipole moment. We explore a wide range of motilities and dipolar coupling strengths and characterize the corresponding behavior based on several order parameters. At low densities and low motilities, the most important structural phenomenon is the aggregation of the dipolar particles into chains. Upon increasing the particle motility, these chain-like structures break, and the system transforms into a weakly correlated isotropic fluid. At high densities, we observe that the motility-induced phase separation is strongly suppressed by the dipolar coupling. Once the dipolar coupling dominates the thermal energy, the phase separation disappears, and the system rather displays a flocking state, where particles form giant clusters and move collective along one direction. We provide arguments for the emergence of the flocking behavior, which is absent in the passive dipolar system.
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Hydrogels constructed with functionalized polysaccharides are of interest in a multitude of applications, chiefly the design of therapeutic and regenerative formulations. Tailoring the chemical modification of polysaccharide-based hydrogels to achieve specific drug release properties involves the optimization of many tunable parameters, including (i) the type, degree (χ), and pattern of the functional groups, (ii) the water-polymer ratio, and (iii) the drug payload. To guide the design of modified polysaccharide hydrogels for drug release, we have developed a computational toolbox that predicts the structure and physicochemical properties of acylated chitosan chains, and their impact on the transport of drug molecules. Herein, we present a multiscale coarse-grained model to investigate the structure of networks of chitosan chains modified with acetyl, butanoyl, or heptanoyl moieties, as well as the diffusion of drugs doxorubicin (Dox) and gemcitabine (Gem) through the resulting networks. The model predicts the formation of different network structures, in particular the hydrophobically-driven transition from a uniform to a cluster/channel morphology and the formation of fibers of chitin chains. The model also describes the impact of structural and physicochemical properties on drug transport, which was confirmed experimentally by measuring Dox and Gem diffusion through an ensemble of modified chitosan hydrogels.
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Quitosano , Hidrogeles , Doxorrubicina , Liberación de Fármacos , PolímerosRESUMEN
The self-assembly of colloidal particles in dynamic environments has become an important field of study because of potential applications in fabricating out-of-equilibrium materials. We investigate the phase behavior of mixtures of passive dipolar colloids and active soft spheres using Brownian dynamics simulations in two dimensions. The phase behaviors exhibited include dipolar percolated network, dipolar string-fluid, isotropic fluid, and a phase-separated state. We find that the clustering of dipolar colloids is enhanced in the presence of slow-moving active particles compared to the clustering of dipolar particles mixed with passive particles. When the active particle motility is high, the chains of dipolar particles are either broken into short chains or pushed into dense clusters. Motility-induced phase separation into dense and dilute phases is also present. The area fraction of particles in the dilute phase increases as the fraction of active particles in the system decreases, while the area fraction of particles in the dense phase remains constant. Our findings are relevant to the development of reconfigurable self-assembled materials.
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We suggest an improved version of the intermediate resolution implicit solvent model for lipids, LIME, that was previously developed for use with discontinuous molecular dynamics (DMD) simulations. LIME gets its geometrical and the energy parameters between bonded and nonbonded pairs of coarse-grained (CG) sites from atomistic simulations. The improved model, LIME 2.0, uses multiple square wells rather than the single square well used in original LIME to obtain intermolecular interactions that more faithfully mimic those from atomistic simulations. The multi-state iterative Boltzmann inversion (MS-IBI) scheme is used to determine the interaction parameters. This means that a single set of interaction parameters between coarse-grained sites can be used to represent the lipid bilayers at different temperatures. The physical properties of CG DSPE lipid bilayer are calculated using CG simulations and compared to atomistic simulations results to verify the improved model. The phase transition temperature of the lipid bilayer is measured accurately and the lipid translocation phenomenon, " flip-flop" is observed through CG simulation. These results suggest that CG parameterization using multiple square-well and the MS-IBI scheme is well suited to the study of lipid bilayers cross a range of temperatures with DMD simulations.
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Mutations in myocilin, predominantly within its olfactomedin (OLF) domain, are causative for the heritable form of open angle glaucoma in humans. Surprisingly, mice expressing Tyr423His mutant myocilin, corresponding to a severe glaucoma-causing mutation (Tyr437His) in human subjects, exhibit a weak, if any, glaucoma phenotype. To address possible protein-level discrepancies between mouse and human OLFs, which might lead to this outcome, biophysical properties of mouse OLF were characterized for comparison with those of human OLF. The 1.55 Å resolution crystal structure of mouse OLF reveals an asymmetric 5-bladed ß-propeller that is nearly indistinguishable from previous structures of human OLF. Wild-type and selected mutant mouse OLFs mirror thermal stabilities of their human OLF counterparts, including characteristic stabilization in the presence of calcium. Mouse OLF forms thioflavin T-positive aggregates with a similar end-point morphology as human OLF, but amyloid aggregation kinetic rates of mouse OLF are faster than human OLF. Simulations and experiments support the interpretation that kinetics of mouse OLF are faster because of a decreased charge repulsion arising from more neutral surface electrostatics. Taken together, phenotypic differences observed in mouse and human studies of mutant myocilin could be a function of aggregation kinetics rates, which would alter the lifetime of putatively toxic protofibrillar intermediates.
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Amiloide/química , Proteínas del Citoesqueleto/química , Proteínas de la Matriz Extracelular/química , Proteínas del Ojo/química , Glaucoma/genética , Glicoproteínas/química , Amiloide/genética , Animales , Cristalografía por Rayos X , Proteínas del Citoesqueleto/genética , Proteínas del Ojo/genética , Glicoproteínas/genética , Humanos , Ratones , Modelos Moleculares , Mutación Puntual , Agregado de Proteínas , Conformación Proteica , Dominios Proteicos , Pliegue de Proteína , Estabilidad ProteicaRESUMEN
Combination chemotherapy with a defined ratio and sequence of drug release is a clinically established and effective route to treat advanced solid tumors. In this context, a growing body of literature demonstrates the potential of hydrogels constructed with chemically modified polysaccharides as depots for controlled release of chemotherapeutics. Identifying the appropriate modification in terms of physicochemical properties of the functional group and its degree of substitution (χ) to achieve the desired release profile for multiple drugs is, however, a complex multivariate problem. To address this issue, we have developed a computational toolbox that models the migration of a drug pair through a hydrated network of polysaccharide chains modified with hydrophobic moieties. In this study, we chose doxorubicin (DOX) and Gemcitabine (GEM) as model drugs, as their synergistic effect against breast cancer has been thoroughly investigated, and chitosan as the model polymer. Our model describes how the modification of chitosan chains with acetyl, butanoyl, and heptanoyl moieties at different values χ governs both the structure of the hydrogel network and drug migration through it. Our experimental data confirm the in silico predictions for both single- and dual-drug release and, most notably, the counterintuitive inversion of release vs χ that occurs when switching from a single- to a dual-drug system. Consensus between predicted and experimental data indicates that acetyl modifications (χ = 32-42%) and butanoyl modifications (χ = 19-24%) provide synergistic GEM/DOX release molar ratios (i.e., 5-10). Collectively, these results demonstrate the potential of this model in guiding the design of chemotherapeutic hydrogels to combat cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Quitosano/química , Portadores de Fármacos/química , Liberación de Fármacos , Sinergismo Farmacológico , Hidrogeles/química , Protocolos de Quimioterapia Combinada Antineoplásica/química , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Doxorrubicina/administración & dosificación , Femenino , Humanos , Polímeros/química , GemcitabinaRESUMEN
The ß roll molecules with sequence (GAGAGAGQ)10 stack via hydrogen bonding to form fibrils which have been themselves been used to make viral capsids of DNA strands, supramolecular nanotapes and pH-responsive gels. Accelerated molecular dynamics (aMD) simulations are used to investigate the unfolding of a stack of two ß roll molecules, (GAGAGAGQ)10, to shed light on the folding mechanism by which silk-inspired polypeptides form fibrils and to identify the dominant forces that keep the silk-inspired polypeptide in a ß roll configuration. Our study shows that a molecule in a stack of two ß roll molecules unfolds in a step-wise fashion mainly from the C terminal. The bottom template is found to play an important role in stabilizing the ß roll structure of the molecule on top by strengthening the hydrogen bonds in the layer that it contacts. Vertical hydrogen bonds within the ß roll structure are considerably weaker than lateral hydrogen bonds, signifying the importance of lateral hydrogen bonds in stabilizing the ß roll structure. Finally, an intermediate structure was found containing a ß hairpin and an anti-parallel ß sheet consisting of strands from the top and bottom molecules, revealing the self-healing ability of the ß roll stack.
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Modelos Químicos , Simulación de Dinámica Molecular , Péptidos/química , Pliegue de Proteína , Seda/química , Seda/ultraestructura , Conformación Proteica , Dominios Proteicos , Desplegamiento ProteicoRESUMEN
Self-assembly of binary mixtures that contain anisotropic, interacting colloidal particles have been proposed as a way to create new, multi-functional materials. We simulate binary mixtures of dipolar rods and dipolar discs in two-dimensions using discontinuous molecular dynamics to determine how the assembled structures of these mixtures differ from those seen in single component systems. Two different binary mixtures are investigated: a mixture of an equal number of dipolar rods and dipolar discs ("equal number"), and a mixture where the area fraction of dipolar rods is equal to the area fraction of dipolar discs ("equal area"). Phase boundaries between fluid, string-fluid, and "gel" phases are calculated and compared to the phase boundaries of the pure components. Looking deeper at the underlying structure of the mixture reveals a complex interplay between the rods and discs and the formation of states where the two components are in different phases. The mixtures exhibit phases where both rods and discs are in the fluid phase, where rods form a string-fluid while discs remain in the fluid phase, a rod string-fluid coexisting with a disc string-fluid, a "gel" that consists primarily of rods while the discs form either a fluid or string-fluid phase, and a "gel" that contains both rods and discs. Our results give insight into the general assembly pathway of binary mixtures, and how complex aggregates can be created by varying the mixture composition, strength of interaction between the two components, and the temperature. By manipulating the properties of one of the components it should be possible to fabricate bifunctional, thermally responsive self-assembled materials.
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The prion diseases are a family of fatal neurodegenerative diseases associated with the misfolding and accumulation of normal prion protein (PrPC) into its pathogenic scrapie form (PrPSc). Understanding the fundamentals of prion protein aggregation and the molecular architecture of PrPSc is key to unraveling the pathology of prion diseases. Our work investigates the early-stage aggregation of three prion protein peptides, corresponding to residues 120-144 of human (Hu), bank vole (BV), and Syrian hamster (SHa) prion protein, from disordered monomers to ß-sheet-rich fibrillar structures. Using 12 µs discontinuous molecular dynamics simulations combined with the PRIME20 force field, we find that the Hu-, BV-, and SHaPrP(120-144) aggregate via multiple nucleation-dependent pathways to form U-shaped, S-shaped, and Ω-shaped protofilaments. The S-shaped HuPrP(120-144) protofilament is similar to the amyloid core structure of HuPrP(112-141) predicted by Zweckstetter. HuPrP(120-144) has a shorter aggregation lag phase than BVPrP(120-144) followed by SHaPrP(120-144), consistent with experimental findings. Two amino acid substitutions I138M and I139M retard the formation of parallel in-register ß-sheet dimers during the nucleation stage by increasing side chain-side chain association and reducing side chain interaction specificity. On average, HuPrP(120-144) aggregates contain more parallel ß-sheet content than those formed by BV- and SHaPrP(120-144). Deletion of the C-terminal residues 138-144 prevents formation of fibrillar structures in agreement with the experiment. This work sheds light on the amyloid core structures underlying prion strains and how I138M, I139M, and S143N affect prion protein aggregation kinetics.
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Amiloide/química , Proteínas PrPC/química , Agregado de Proteínas , Animales , Arvicolinae , Cricetinae , Humanos , Mesocricetus , Estructura Secundaria de ProteínaRESUMEN
The statistical associating fluid theory for potentials of variable range (SAFT-VR) is used to predict the fluid phase behavior of elastin-like polypeptide (ELP) sequences in aqueous solution with special focus on the loci of lower critical solution temperatures (LCSTs). A SAFT-VR model for these solutions is developed following a coarse-graining approach combining information from atomistic simulations and from previous SAFT models for previously reported relevant systems. Constant-pressure temperature-composition phase diagrams are determined for solutions of (VPGVG)n sequences + water with n = 1 to 300. The SAFT-VR equation of state lends itself to the straightforward calculation of phase boundaries so that complete fluid-phase equilibria can be calculated efficiently. A broad range of thermodynamic conditions of temperature and pressure are considered, and regions of vapor-liquid and liquid-liquid coexistence, including LCSTs, are found. The calculated phase boundaries at low concentrations match those measured experimentally. The temperature-composition phase diagrams of the aqueous ELP solutions at low pressure (0.1 MPa) are similar to those of types V and VI phase behavior in the classification of Scott and van Konynenburg. An analysis of the high-pressure phase behavior confirms, however, that a closed-loop liquid-liquid immiscibility region, separate from the gas-liquid envelope, is present for aqueous solutions of (VPGVG)30; such a phase diagram is typical of type VI phase behavior. ELPs with shorter lengths exhibit both liquid-liquid and gas-liquid regions, both of which become less extensive as the chain length of the ELP is decreased. The strength of the hydrogen-bonding interaction is also found to affect the phase diagram of the (VPGVG)30 system in that the liquid-liquid and gas-liquid regions expand as the hydrogen-bonding strength is decreased and shrink as it is increased. The LCSTs of the mixtures are seen to decrease as the ELP chain length is increased.