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Short peptides are attractive building blocks for the fabrication of self-assembled materials with significant biological, chemical, and physical properties. The microscopic and macroscopic properties of assemblies are usually closely related to the dimensionality of formed hydrogen bond networks. Here, two completely different supramolecular architectures connected by distinct hydrogen bond networks were obtained by simply adding a hydroxyl group to switch from cyclo-tryptophan-alanine (cyclo-WA) to cyclo-tryptophan-serine (cyclo-WS). While hydroxyl-bearing cyclo-WS molecules provided an additional hydrogen bond donor that links to adjacent molecules, forming a rigid three-dimensional network, cyclo-WA arranged into a water-mediated zipper-like structure with a softer two-dimensional layer template. This subtle alteration resulted in a 14-fold enhancement of Young's modulus values in cyclo-WS compared to cyclo-WA. Both cyclo-dipeptides exhibit biocompatibility, high fluorescence, and piezoelectricity. The demonstrated role of dimensionality of hydrogen bond networks opens new avenues for rational design of materials with precise morphologies and customizable properties for bioelectronic applications.
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Crystal nucleation shapes the structure and product size distribution of solid-state pharmaceuticals and is seeded by early-stage molecular self-assemblies formed in host solution. Here, molecular clustering of salicylamide in ethyl acetate, methanol, and acetonitrile was investigated using photon correlation spectroscopy. Cluster size steadily increased over 3 days and with concentration across the range from undersaturated to supersaturated solutions. Solute concentration normalized by solubility provided more sensitive characterization of molecular-level conditions than concentration alone. In saturated solution, cluster size is independent of solvent, while at equal supersaturation, solvent-dependent cluster size increases as methanol < acetonitrile < ethyl acetate, commensurate with increasing nucleation propensity. In ethyl acetate, with largest prenucleation clusters, the driving force required for nucleation is lowest, compared to methanol with smallest clusters and highest driving force. To understand solvent-solute effects, we performed IR spectroscopy supported by molecular simulations. We observe solute-solvent interaction weakening in the same order: methanol < acetonitrile < ethyl acetate, quantifying the weaker solvent-solute interactions that permit the formation of larger prenucleation clusters. Our results support the hypothesis that nucleation is easier in weaker solvents because weak solute-solvent interactions favor growth of large clusters, as opposed to relying solely on ease of desolvation.
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Sulfonic acid-containing bioorganic monomers with wide molecular designability and abundant hydrogen bonding sites hold great potential to design diverse functional biocrystals but have so far not been explored for piezoelectric energy harvesting applications due to the lack of strategies to break the centrosymmetry of their assemblies. Here, a significant molecular packing transformation from centrosymmetric into non-centrosymmetric conformation by the addition of an amide terminus in the sulfonic acid-containing bioorganic molecule is demonstrated, allowing a high electromechanical response. The amide-functionalized molecule self-assembles into a polar supramolecular parallel ß-sheet-like structure with a high longitudinal piezoelectric coefficient d11 = 15.9 pm V-1 that produces the maximal open-circuit voltage of >1 V and the maximal power of 18 nW in nanogenerator devices pioneered. By contrast, molecules containing an amino or a cyclohexyl terminus assemble into highly symmetric 3D hydrogen bonding diamondoid-like networks or 2D double layer structures that show tunable morphologies, thermostability, and mechanical properties but non-piezoelectricity. This work not only presents a facile approach to achieving symmetry transformation of bioorganic assemblies but also demonstrates the terminal group and the property correlation for tailor-made design of high-performance piezoelectric biomaterials.
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Highly-efficient molecular photoswitching occurs ex-situ but not to-date inside electronic devices due to quenching of excited states by background interactions. Here we achieve fully reversible in-situ mechano-optoelectronic switching in self-assembled monolayers (SAMs) of tetraphenylethylene molecules by bending their supporting electrodes to maximize aggregation-induced emission (AIE). We obtain stable, reversible switching across >1600 on/off cycles with large on/off ratio of (3.8 ± 0.1) × 103 and 140 ± 10 ms switching time which is 10-100× faster than other approaches. Multimodal characterization shows mechanically-controlled emission with UV-light enhancing the Coulomb interaction between the electrons and holes resulting in giant enhancement of molecular conductance. The best mechano-optoelectronic switching occurs in the most concave architecture that reduces ambient single-molecule conformational entropy creating artificially-tightened supramolecular assemblies. The performance can be further improved to achieve ultra-high switching ratio on the order of 105 using tetraphenylethylene derivatives with more AIE-active sites. Our results promise new applications from optimized interplay between mechanical force and optics in soft electronics.
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Cyclophosphazenes offer a robust and easily modifiable platform for a diverse range of functional systems that have found applications in a wide variety of areas. Herein, for the first time, it reports an organophosphazene-based supramolecular ferroelectric [(PhCH2 NH)6 P3 N3 Me]I, [PMe]I. The compound crystallizes in the polar space group Pc and its thin-film sample exhibits remnant polarization of 5 µC cm-2 . Vector piezoresponse force microscopy (PFM) measurements indicated the presence of multiaxial polarization. Subsequently, flexible composites of [PMe]I are fabricated for piezoelectric energy harvesting applications using thermoplastic polyurethane (TPU) as the matrix. The highest open-circuit voltages of 13.7 V and the maximum power density of 34.60 µW cm-2 are recorded for the poled 20 wt.% [PMe]I/TPU device. To understand the molecular origins of the high performance of [PMe]I-based mechanical energy harvesting devices, piezoelectric charge tensor values are obtained from DFT calculations of the single crystal structure. These indicate that the mechanical stress-induced distortions in the [PMe]I crystals are facilitated by the high flexibility of the layered supramolecular assembly.
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Dynamic photoactuating crystals have become a sensation due to their potential applications in developing smart medical devices, molecular machines, artificial muscles, flexible electronics actuators, probes and microrobots. Here we report the synthesis of two iso-structural metal-organic crystals, [Zn(4-ohbz)2(4-nvp)2] (1) and [Cd(4-ohbz)2(4-nvp)2] (2) {H4-ohbz = 4-hydroxy benzoic acid; 4-nvp = 4-(1-naphthylvinyl)pyridine} which undergo topochemical [2 + 2] cycloaddition under UV irradiation as well as sunlight to generate a dimerized product of discrete metal-complex [Zn(4-ohbz)2(rctt-4-pncb)] {rctt-4-pncb = 1,3-bis(4'-pyridyl)-2,4-bis(naphthyl)cyclobutane} (1') and one-dimensional coordination polymer (1D CP) [Cd(4-ohbz)2(rctt-4-pncb)] (2') respectively, in a single-crystal-to-single-crystal (SCSC) process. The Zn-based compound demonstrates photosalient behaviour, wherein crystals show jumping, splitting, rolling, and swelling upon UV irradiation. However, the Cd-based crystals do not show such behaviour maintaining the initial supramolecular packing and space group. Thus the photomechanical behaviour can be induced by choosing a suitable metal ion. The above findings are thoroughly validated by quantitative density functional theory (DFT) calculations which show that the Zn-based crystal shifts towards an orthorhombic structure to resolve the anisotropic UV-induced mechanical strain. Furthermore, the mechano-structure-property relationship has been established by complimentary nanoindentation measurements, which are in-line with the DFT-predicted single crystal values.
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The potential of ultra-short peptides to self-assemble into well-ordered functional nanostructures makes them promising minimal components for mimicking the basic ingredient of nature and diverse biomaterials. However, selection and modular design of perfect de novo sequences are extremely tricky due to their vast possible combinatorial space. Moreover, a single amino acid substitution can drastically alter the supramolecular packing structure of short peptide assemblies. Here, we report the design of rigid hybrid hydrogels produced by sequence engineering of a new series of ultra-short collagen-mimicking tripeptides. Connecting glycine with different combinations of proline and its post-translational product 4-hydroxyproline, the single triplet motif, displays the natural collagen-helix-like structure. Improved mechanical rigidity is obtained via co-assembly with the non-collagenous hydrogelator, fluorenylmethoxycarbonyl (Fmoc) diphenylalanine. Characterizations of the supramolecular interactions that promote the self-supporting and self-healing properties of the co-assemblies are performed by physicochemical experiments and atomistic models. Our results clearly demonstrate the significance of sequence engineering to design functional peptide motifs with desired physicochemical and electromechanical properties and reveal co-assembly as a promising strategy for the utilization of small, readily accessible biomimetic building blocks to generate hybrid biomolecular assemblies with structural heterogeneity and functionality of natural materials.
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Hidrogéis , Peptídeos , Hidrogéis/química , Hidroxiprolina , Peptídeos/química , Materiais Biocompatíveis/química , Colágeno , GlicinaRESUMO
BACKGROUND: Natural cellulosome multi-enzyme complexes, their components, and engineered 'designer cellulosomes' (DCs) promise an efficient means of breaking down cellulosic substrates into valuable biofuel products. Their broad uptake in biotechnology relies on boosting proximity-based synergy among the resident enzymes, but the modular architecture challenges structure determination and rational design. RESULTS: We used small angle X-ray scattering combined with molecular modeling to study the solution structure of cellulosomal components. These include three dockerin-bearing cellulases with distinct substrate specificities, original scaffoldins from the human gut bacterium Ruminococcus champanellensis (ScaA, ScaH and ScaK) and a trivalent cohesin-bearing designer scaffoldin (Scaf20L), followed by cellulosomal complexes comprising these components, and the nonavalent fully loaded Clostridium thermocellum CipA in complex with Cel8A from the same bacterium. The size analysis of Rg and Dmax values deduced from the scattering curves and corresponding molecular models highlight their variable aspects, depending on composition, size and spatial organization of the objects in solution. CONCLUSIONS: Our data quantifies variability of form and compactness of cellulosomal components in solution and confirms that this native plasticity may well be related to speciation with respect to the substrate that is targeted. By showing that scaffoldins or components display enhanced compactness compared to the free objects, we provide new routes to rationally enhance their stability and performance in their environment of action.
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The apparent piezoelectricity of biological materials is not yet fully understood at the molecular level. In particular, dynamic noncovalent interactions, such as host-guest binding, are not included in the classical piezoelectric model, which limits the rational design of eco-friendly piezoelectric supramolecular materials. Here, inspired by the conformation-dependent mechanoresponse of the Piezo channel proteins, we show that guest-host interactions can amplify the electromechanical response of a conformationally mobile peptide metal-organic framework (MOF) based on the endogenous carnosine dipeptide, demonstrating a new type of adaptive piezoelectric supramolecular material. Density functional theory (DFT) predictions validated by piezoresponse force microscopy (PFM) measurements show that directional alignment of the guest molecules in the host carnosine-zinc peptide MOF channel determines the macroscopic electromechanical properties. We produce stable, robust 1.4 V open-circuit voltage under applied force of 25 N with a frequency of 0.1 Hz. Our findings demonstrate that the regulation of host-guest interactions could serve as an efficient method for engineering sustainable peptide-based power generators.
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Carnosina , Estruturas Metalorgânicas , Microscopia de Força Atômica , Conformação Molecular , Compostos OrgânicosRESUMO
Electrochemical, spectroscopic and computational methods are used to demonstrate that electrified aqueous|organic interfaces are a suitable bio-mimetic platform to study and contrast the accelerated electrocatalytic activity of cytochrome c towards the production of reactive oxygen species (ROS) in the presence of denaturing agents such as guanidinium chloride and urea.
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Citocromos c , Água , Citocromos c/química , Guanidina/química , Espécies Reativas de Oxigênio , Ureia/química , Água/químicaRESUMO
Programmed cell death via apoptosis is a natural defence against excessive cell division, crucial for fetal development to maintenance of homeostasis and elimination of precancerous and senescent cells. Here, we demonstrate an electrified liquid biointerface that replicates the molecular machinery of the inner mitochondrial membrane at the onset of apoptosis. By mimicking in vivo cytochrome c (Cyt c) interactions with cell membranes, our platform allows us to modulate the conformational plasticity of the protein by simply varying the electrochemical environment at an aqueous-organic interface. We observe interfacial electron transfer between an organic electron donor decamethylferrocene and O2, electrocatalyzed by Cyt c. This interfacial reaction requires partial Cyt c unfolding, mimicking Cyt c in vivo peroxidase activity. As proof of concept, we use our electrified liquid biointerface to identify drug molecules, such as bifonazole, that can potentially down-regulate Cyt c and protect against uncontrolled neuronal cell death in neurodegenerative disorders.
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The dynamics and spectroscopy of N-methyl-acetamide (NMA) and trialanine in solution are characterized from molecular dynamics simulations using different energy functions, including a conventional point charge (PC)-based force field, one based on a multipolar (MTP) representation of the electrostatics, and a semiempirical DFT method. For the 1D infrared spectra, the frequency splitting between the two amide-I groups is 10 cm-1 from the PC, 13 cm-1 from the MTP, and 47 cm-1 from self-consistent charge density functional tight-binding (SCC-DFTB) simulations, compared with 25 cm-1 from experiment. The frequency trajectory required for the frequency fluctuation correlation function (FFCF) is determined from individual normal mode (INM) and full normal mode (FNM) analyses of the amide-I vibrations. The spectroscopy, time-zero magnitude of the FFCF C(t = 0), and the static component Δ02 from simulations using MTP and analysis based on FNM are all consistent with experiments for (Ala)3. Contrary to this, for the analysis excluding mode-mode coupling (INM), the FFCF decays to zero too rapidly and for simulations with a PC-based force field, the Δ02 is too small by a factor of two compared with experiments. Simulations with SCC-DFTB agree better with experiment for these observables than those from PC-based simulations. The conformational ensemble sampled from simulations using PCs is consistent with the literature (including PII, ß, αR, and αL), whereas that covered by the MTP-based simulations is dominated by PII with some contributions from ß and αR. This agrees with and confirms recently reported Bayesian-refined populations based on 1D infrared experiments. FNM analysis together with a MTP representation provides a meaningful model to correctly describe the dynamics of hydrated trialanine.
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Alanina , Amidas , Teorema de Bayes , Conformação Molecular , Simulação de Dinâmica Molecular , Análise EspectralRESUMO
Realization of a self-assembled, nontoxic and eco-friendly piezoelectric device with high-performance, sensitivity and reliability is highly desirable to complement conventional inorganic and polymer based materials. Hierarchically organized natural materials such as collagen have long been posited to exhibit electromechanical properties that could potentially be amplified via molecular engineering to produce technologically relevant piezoelectricity. Here, by using a simple, minimalistic, building block of collagen, we fabricate a peptide-based piezoelectric generator utilising a radically different helical arrangement of Phe-Phe-derived peptide, Pro-Phe-Phe and Hyp-Phe-Phe, based only on proteinogenic amino acids. The simple addition of a hydroxyl group increases the expected piezoelectric response by an order of magnitude (d35 = 27 pm V-1). The value is highest predicted to date in short natural peptides. We demonstrate tripeptide-based power generator that produces stable max current >50 nA and potential >1.2 V. Our results provide a promising device demonstration of computationally-guided molecular engineering of piezoelectricity in peptide nanotechnology.
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Fontes de Energia Bioelétrica , Materiais Biomiméticos/química , Biomimética/métodos , Engenharia Química/métodos , Oligopeptídeos/química , Materiais Biomiméticos/metabolismo , Colágeno/química , Desenho Assistido por Computador , Microscopia Eletrônica de Transmissão , Simulação de Dinâmica Molecular , Oligopeptídeos/metabolismo , Conformação Proteica em alfa-Hélice , Reprodutibilidade dos Testes , Difração de Raios XRESUMO
Aromatic molecules such as pyrenes are a unique class of building units for graphene functionalization, forming highly ordered π-π stacks while peptides provide more complex, biocompatible linkers. Understanding the adsorption and stacking behavior of these molecules and their influence on material properties is an essential step in enabling highly repeatable 2D material-based applications, such as biosensors, gas sensors, and solar cells. In this work, we characterize pyrene and peptide self-assembly on graphene substrates using fluorescence microscopy, atomic force microscopy and electrolyte-gated field-effect measurements supported by quantum mechanical calculations. We find distinct binding and assembly modes for pyrenes versus peptides with corresponding distinct electronic signatures in their characteristic charge neutrality point and field-effect slope responses. Our data demonstrates that pyrene- and peptide-based self-assembly platforms can be highly beneficial for precisely customizing graphene electronic properties for desired device technologies such as transport-based biosensing graphene field-effect transistors.
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Grafite/química , Peptídeos/química , Pirenos/química , Transistores Eletrônicos , Eletrólitos/química , Elétrons , Microscopia de Força Atômica , Microscopia de Fluorescência , Imagem Óptica , Tamanho da Partícula , Peptídeos/síntese química , Pirenos/síntese química , Propriedades de SuperfícieRESUMO
Monte Carlo (MC) and molecular dynamics (MD) computer simulations were used to investigate the role of adsorption during seeded and heterogeneous crystallization. The simulations characterized the range of adsorption energies and configurations encountered during adsorption of individual molecules of active pharmaceutical ingredients (APIs), with varying hydrogen-bonding tendencies, onto seed and heterosurfaces. Specifically, the adsorption of acetaminophen (AAP), carbamazepine (CBMZ), fenofibrate (FF), phenylbutazone (PBZ), clozapine (CPB), and risperidone (RIS) was simulated on selected crystallographic facets of their own crystals as examples of seeded crystallizations and on lactose or microcrystalline cellulose (MCC) substrates as heterosurfaces. The MC screening provided adsorption enthalpies in the range of -59 to -155 kJ mol-1 for these APIs on lactose, generally increasing as the molar mass of the API increased. The corresponding values predicted for adsorption of each API onto its own crystal were in the range of -92 to -201 kJ mol-1. More detailed MD simulations performed in methanol showed adsorption free energies for RIS on MCC in the range of -37 to -50 kJ mol-1 with strong molecule-surface complexation lifetime of tens of nanoseconds on the (010) face of MCC. This extended lifetime is a key feature in understanding the mechanism of heterogeneous crystallization. A well-formed nucleus is generated on the surface starting with a single adsorbed molecule. Individual or small clusters add to the adsorbed species. This addition is facilitated by the extended lifetime of the adsorbed molecule, which is several orders of magnitude greater than the time required for additional molecules to assemble and grow into a stable nucleus attached to the heterosurface.
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Diphenylalanine (FF) represents the simplest peptide building block that self-assembles into ordered nanostructures with interesting physical properties. Among self-assembled peptide structures, FF nanotubes display notable stiffness and piezoelectric parameters (Young's modulus = 19-27 GPa, strain coefficient d33 = 18 pC/N). Yet, inorganic alternatives remain the major materials of choice for many applications due to higher stiffness and piezoelectricity. Here, aiming to broaden the applications of the FF motif in materials chemistry, we designed three phenyl-rich dipeptides based on the ß,ß-diphenyl-Ala-OH (Dip) unit: Dip-Dip, cyclo-Dip-Dip, and tert-butyloxycarbonyl (Boc)-Dip-Dip. The doubled number of aromatic groups per unit, compared to FF, produced a dense aromatic zipper network with a dramatically improved Young's modulus of â¼70 GPa, which is comparable to aluminum. The piezoelectric strain coefficient d33 of â¼73 pC/N of such assembly exceeds that of poled polyvinylidene-fluoride (PVDF) polymers and compares well to that of lead zirconium titanate (PZT) thin films and ribbons. The rationally designed π-π assemblies show a voltage coefficient of 2-3 Vm/N, an order of magnitude higher than PVDF, improved thermal stability up to 360 °C (â¼60 °C higher than FF), and useful photoluminescence with wide-range excitation-dependent emission in the visible region. Our data demonstrate that aromatic groups improve the rigidity and piezoelectricity of organic self-assembled materials for numerous applications.
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Nanoestruturas , Fenilalanina , Dipeptídeos , PeptídeosRESUMO
Functionalized cyclodextrin molecules assemble into a wide variety of superstructures in solution, which are of interest for drug delivery and other nanomaterial and biomaterial applications. Here we use a combined simulation and experimental approach to probe the coassembly of siRNA and cationic cyclodextrin (c-CD) derivatives into a highly stable gene delivery nanostructure. The c-CD form supramolecular structures via interdigitation of their aliphatic tails, analogous to the formation of lipid bilayers and micelles. The native conformation of siRNA is preserved by the encapsulating c-CD superstructure in an extensive hydrogen-bonding network between the positively charged side arms of c-CD and the negatively charged siRNA backbone. The stability of the complexation is confirmed using isothermal titration calorimetry, and the experimental/simulation codesign methodology opens new avenues for creation of highly engineerable gene delivery vectors.
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Portadores de Fármacos/química , Composição de Medicamentos/métodos , Nanoestruturas/química , RNA Interferente Pequeno/química , beta-Ciclodextrinas/química , Calorimetria , Cátions/química , Estabilidade de Medicamentos , Técnicas de Transferência de Genes , Temperatura Alta , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Eletricidade Estática , Tensoativos/químicaRESUMO
The cellulosome provides a fully worked out example of evolved radical nanotechnology. Improved understanding, and first steps toward re-engineering this biological nanomachine, is providing design rules for the formulation of advanced synthetic materials that can harness molecular flexibility and sticking interactions for applications in clean energy, environmental monitoring, and miniaturized devices. Computer simulations provide atomic scale insights into the mechanical stability of the component protein units, flexibility of short peptides that tether the units into scaffolds, and thermodynamic stability of protein-protein and protein-carbohydrate complexes, complementing and in some cases directing experiments. In the present work, a systematic computational study of cohesin-dockerin pairs, the strongly-bound protein complexes that glue the cellulosome nano-architecture in place, reveals that a short alpha-helix in the middle of the smaller dockerin protein becomes disordered at elevated temperatures and weakens cohesin-dockerin binding in mesophilic species. In thermophilic species, a more extensive and more thermally resistant H-bond network ensures the structure remains ordered at elevated temperatures of up to 400 K. The simulations predict that simply grafting the most crucial eight-residue peptide sequence into the mesophilic complex can, for one species and one of two possible binding modes, potentially create a new thermally resistant complex, providing leads for future experiments to re-engineer designer cellulosomes that can withstand elevated temperatures and so provide clean, renewable biocatalysts.
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The conversion of cellulosic biomass into biofuels requires degradation of the biomass into fermentable sugars. The most efficient natural cellulase system for carrying out this conversion is an extracellular multi-enzymatic complex named the cellulosome. In addition to temperature and pH stability, mechanical stability is important for functioning of cellulosome domains, and experimental techniques such as Single Molecule Force Spectroscopy (SMFS) have been used to measure the mechanical strength of several cellulosomal proteins. Molecular dynamics computer simulations provide complementary atomic-resolution quantitative maps of domain mechanical stability for identification of experimental leads for protein stabilization. In this study, we used multi-scale steered molecular dynamics computer simulations, benchmarked against new SMFS measurements, to measure the intermolecular contacts that confer high mechanical stability to a family 3 Carbohydrate Binding Module protein (CBM3) derived from the archetypal Clostridium thermocellum cellulosome. Our data predicts that electrostatic interactions in the calcium binding pocket modulate the mechanostability of the cellulose-binding module, which provides an additional design rule for the rational re-engineering of designer cellulosomes for biotechnology. Our data offers new molecular insights into the origins of mechanostability in cellulose binding domains and gives leads for synthesis of more robust cellulose-binding protein modules. On the other hand, simulations predict that insertion of a flexible strand can promote alternative unfolding pathways and dramatically reduce the mechanostability of the carbohydrate binding module, which gives routes to rational design of tailormade fingerprint complexes for force spectroscopy experiments.
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Proteínas de Bactérias/química , Cálcio/química , Celulase/química , Simulação de Dinâmica Molecular , Complexos Multienzimáticos/química , Fenômenos Biomecânicos , Cátions Bivalentes , Ligação Proteica , Conformação Proteica , Zinco/químicaRESUMO
Transformation of cellulose into monosaccharides can be achieved by hydrolysis of the cellulose chains, carried out by a special group of enzymes known as cellulases. The enzymatic mechanism of cellulases is well described, but the role of non-enzymatic components of the cellulose-degradation machinery is still poorly understood, and difficult to measure using experiments alone. In this study, we use a comprehensive set of atomistic molecular dynamics simulations to probe the molecular details of binding of the family-3a carbohydrate-binding module (CBM3a) and the bacterial expansin protein (EXLX1) to a range of cellulose substrates. Our results suggest that CBM3a behaves in a similar way on both crystalline and amorphous cellulose, whereas binding of the dual-domain expansin protein depends on the substrate crystallinity, and we relate our computed binding modes to the experimentally measured features of CBM and expansin action on cellulose.