Turn Conformation Research Articles

Geometric descriptors for beta turns.

Beta turns, in which the protein backbone abruptly changes direction over four amino acid residues, are the most common type of protein secondary structure after alpha helices and beta sheets and play key structural and functional roles. Previous work has produced classification systems for turn geometry at multiple levels of precision, but these operate in backbone dihedral-angle (Ramachandran) space, and the absence of a local Euclidean-space coordinate system and structural alignment for turns, or of any systematic Euclidean-space characterization of turn backbone shape, presents challenges for the visualization, comparison and analysis of the wide range of turn conformations and the design of turns and the structures that incorporate them. This work derives a turn-local coordinate system that implicitly aligns turns, together with a set of geometric descriptors that characterize the bulk BB shapes of turns and describe modes of structural variation not explicitly captured by existing systems. These modes are shown to be meaningful by the demonstration of clear relationships between descriptor values and the electrostatic energy of the beta-turn H-bond, the overrepresentations of key side-chain motifs, and the structural contexts of turns. Geometric turn descriptors complement Ramachandran-space classifications, and they can be used to select turn structures for compatibility with particular side-chain interactions or contexts. Potential applications include protein design and other tasks in which an enhanced Euclidean-space characterization of turns may improve understanding or performance. The web-based tools ExploreTurns, MapTurns, and ProfileTurn, available at www.betaturn.com, incorporate turn-local coordinates and turn descriptors and demonstrate their utility.

Evaluation of the influence of ph modification on food proteins structure by FT-IR AND AFM

Objective: The related research of proteins is important due to their wide applications in food science. The aim of this study was to evaluate the influence of pH variation (3.6, 4.6 and 5.6) on morphometric parameters and the secondary structure of proteins (ovalbumin and gliadin). The arithmetic mean roughness (Ra) and agglomerate size (AS) of the proteins were analyzed by atomic force microscopy (AFM), while their secondary structure was analyzed. Design/methodology/approach: by Fourier transform infrared spectroscopy (FT-IR), both at different pH. Subsequently, a correlation analysis of the morphometric changes of the proteins with their secondary structure was performed. Results: Highlighting that it was found that, protein agglomerate size is influenced by changes in β-sheets and turn conformations. Findings/conclusions: The novelty of this contribution consists in demonstrating that there is a close structure-functionality relationship between the morphometric parameters of proteins and their secondary structure, combining microscopy and spectroscopy techniques. This allows a clear and deep understanding of protein behavior to select the appropriate pH conditions to improve the properties of many foods.

DON/DRP-104 as potent serine protease inhibitors implicated in SARS-CoV-2 infection: Comparative binding modes with human TMPRSS2 and novel therapeutic approach.

Human transmembrane serine protease 2 (TMPRSS2) is an important member of the type 2 transmembrane serine protease (TTSP) family with significant therapeutic markings. The search for potent TMPRSS2 inhibitors against severe acute respiratory syndrome coronavirus 2 infection with favorable tissue specificity and off-site toxicity profiles remains limited. Therefore, probing the anti-TMPRSS2 potential of enhanced drug delivery systems, such as nanotechnology and prodrug systems, has become compelling. We report the first in silico study of TMPRSS2 against a prodrug, [isopropyl(S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)-propanamido)-6-diazo-5-oxo-hexanoate] also known as DRP-104 synthesized from 6-Diazo-5-oxo-l-norleucine (DON). We performed comparative studies on DON and DRP-104 against a clinically potent TMPRSS2 inhibitor, nafamostat, and a standard serine protease inhibitor, 4-(2-Aminoethyl) benzenesulfonyl fluoride (AEBSF) against TMPRSS2 and found improved TMPRSS2 inhibition through synergistic binding of the S1/S1' subdomains. Both DON and DRP-104 had better thermodynamic profiles than AEBSF and nafamostat. DON was found to confer structural stability with strong positive correlated inter-residue motions, whereas DRP-104 was found to confer kinetic stability with restricted residue displacements and reduced loop flexibility. Interestingly, the Scavenger Receptor Cysteine-Rich (SRCR) domain of TMPRSS2 may be involved in its inhibition mechanics. Two previously unidentified loops, designated X (270-275) and Y (293-296) underwent minimal and major structural transitions, respectively. In addition, residues 273-277 consistently transitioned to a turn conformation in all ligated systems, whereas unique transitions were identified for other transitioning residue groups in each TMPRSS2-inhibitor complex. Intriguingly, while both DON and DRP-104 showed similar loop transition patterns, DRP-104 preserved loop structural integrity. As evident from our systematic comparative study using experimentally/clinically validated inhibitors, DRP-104 may serve as a potent and novel TMPRSS2 inhibitor and warrants further clinical investigation.

Emerging role of carbonyl-carbonyl interactions in the classification of beta turns.

Carbonyl-carbonyl interactions in peptides and proteins attracted considerable interest in recent years. Here, we report a survey of carbonyl-carbonyl interactions in cyclic peptides, depsipeptides, peptoids and discuss the relationship between backbone torsion angles and CO∙∙∙CO distances. In general, φ values in the range between -40° and -90° and between 40° and 90° correspond to CO∙∙∙CO distances below 3.22 Å. By extending the analysis of carbonyl-carbonyl interactions in different types of beta turns in proteins, we also highlight the role of direct or reciprocal carbonyl-carbonyl interactions in stabilizing the beta turn conformation for each specific type. We confirmed the new type II beta turn, detected by Dunbrack and coworkers, and named Pa, and detect the presence of a direct carbonyl-carbonyl interaction between the second and third residues of the turn. We also evidenced the existence of another new type II beta turn, named pA (following Dunbrack's notation), which represents the alternative conformation of Pa with opposite φ and ψ values and is characterized by a direct carbonyl-carbonyl interaction between the second and third residues of the turn. Finally, we show that the occurrence of CO∙∙∙CO interactions could be also advocated to explain from a chemical point of view the diversity of turn types.

Peptide Stereochemistry Effects from pKa-Shift to Gold Nanoparticle Templating in a Supramolecular Hydrogel.

The divergent supramolecular behavior of a series of tripeptide stereoisomers was elucidated through spectroscopic, microscopic, crystallographic, and computational techniques. Only two epimers were able to effectively self-organize into amphipathic structures, leading to supramolecular hydrogels or crystals, respectively. Despite the similarity between the two peptides' turn conformations, stereoconfiguration led to different abilities to engage in intramolecular hydrogen bonding. Self-assembly further shifted the pKa value of the C-terminal side chain. As a result, across the pH range 4-6, only one epimer predominated sufficiently as a zwitterion to reach the critical molar fraction, allowing gelation. By contrast, the differing pKa values and higher dipole moment of the other epimer favored crystallization. The four stereoisomers were further tested for gold nanoparticle (AuNP) formation, with the supramolecular hydrogel being the key to control and stabilize AuNPs, yielding a nanocomposite that catalyzed the photodegradation of a dye. Importantly, the AuNP formation occurred without the use of reductants other than the peptide, and the redox chemistry was investigated by LC-MS, NMR, and infrared scattering-type near field optical microscopy (IR s-SNOM). This study provides important insights for the rational design of simple peptides as minimalistic and green building blocks for functional nanocomposites.

Designer pseudopeptides: autofluorescent polygonal tubes via Phe-zipper and triple helix.

Chemists are increasingly turning to biology for inspiration to develop novel and superior synthetic materials. Here, we present an innovative peptide design strategy for tubular assembly. In this simple design, a phenylene urea unit is introduced as an aglet at the N-terminus of the peptide. When α-amino isobutyric acid (Aib) is the first residue and phenylalanine (Phe) is the second residue from the phenylene urea entity, it induces an edge-to-face π-π interaction resulting in a turn conformation. The peptides with a unique reverse turn conformation associate to form polygonal peptide tubes via a Phe-zipper arrangement, as evidenced by microscopic and single crystal X-ray studies. Ultra-microscopic imaging revealed that the tubular assembly is hexagonal, square, and triangular in shape. This hierarchical assembly reveals the interplay between π-π interactions and hydrogen bonding. In another design, pseudopeptide 5, wherein a Phe-Phe (FF) unit is linked to phenylene urea, formed polygonal tubes via a triple helical arrangement. Interestingly, the extension of this design to the bis-urea core resulted in vesicular assembly. These supramolecular polygonal tubes and vesicles showed autofluorescence, which allowed confocal imaging. The observed fluorescence is an additional advantage for applications in biological and medical sciences.

An accurate DFT study within conformational survey of the d-form serine−alanine protected dipeptide

The conformational analysis of n-formyl-d-serine-d-alanine-NH2 dipeptide was studied using density functional theory methods at B3LYP, B3LYP‒D3, and M06‒2X levels using 6‒311 + G (d,p) basis set in the gas and water phases. 87 conformers of 243 stable ones were located and the rest of them were migrated to the more stable geometries. Migration pattern suggests the more stable dipeptide model bears serine in βL, γD, γL and the alanine in γL and γD configurations. The investigation of side‒chain‒backbone interactions revealed that the most stable conformer, γD–γL, is in the β‒turn region of Ramachandran map; therefore, serine-alanine dipeptide model should be adopted with a β‒turn conformation. Intramolecular hydrogen bonding in β‒turns consideration by QTAIM disclosed γD–γL includes three hydrogen bonds. The computed UV‒Vis spectrum alongside of NBO calculation showed the five main electronic transition bands derived of n → n* of intra‒ligand alanine moiety of dipeptide structure.

Exploring the Barriers in the Aggregation of a Hexadecameric Human Prion Peptide through the Markov State Model.

The prefibrillar aggregation kinetics of prion peptides are still an enigma. In this perspective, we employ atomistic molecular dynamics (MD) simulations of the shortest human prion peptide (HPP) (127GYMLGS132) at various temperatures and peptide concentrations and apply the Markov state model to determine the various intermediates and lag phases. Our results reveal that the natural mechanism of prion peptide self-assembly in the aqueous phase is impeded by two significant kinetic barriers with oligomer sizes of 6-9 and 12-13 peptides, respectively. The first one is the aggregation of unstructured lower-order oligomers, and the second is fibril nucleation, which impedes the further growth of prion aggregates. Among these two activation barriers, the second one is found to be dominant irrespective of the increase in temperature and peptide concentration. These lag phases are captured in all three different force-field parameters, namely, GROMOS-54a7, AMBER-99SB-ILDN, and CHARMMS 36m, at different concentrations. The GROMOS-54a7 and AMBER-99SB-ILDN force fields showed a comparatively higher percentage of β-sheet formation in the metastable aggregate that evolved during the aggregation process. In contrast, the CHARMM-36m force field showed mostly coil or turn conformations. The addition of a novel catecholamine derivative (naphthoquinone dopamine (NQDA)) arrests the aggregation process between the lag phases by increasing the activation barrier for the Lag1 and Lag2 phases in all of the force fields, which further validates the existence of these lag phases. The preferential binding of NQDA with the peptides increases the hydration of peptides and eventually disrupts the organized morphology of prefibrillar aggregates. It reduces the dimer dissociation energy by -24.34 kJ/mol.

Evaluation of the influence of pH modification on food proteins struc-ture by FT-IR and AFM

Objective: The aim of this study was to evaluate the influence of pH variation (3.6, 4.6 and 5.6) on morphometric parameters and the secondary structure of proteins (ovalbumin and gliadin). Design/methodology/approach: The arithmetic mean roughness (Ra) and agglomerate size (AS) of the proteins were analyzed by atomic force microscopy (AFM), while their secondary structure was analyzed by Fourier transform infrared spectroscopy (FT-IR), both at different pH. Subsequently, a correlation analysis of the morphometric changes of the proteins with their secondary structure was performed. Results: Highlighting that it was found that, protein agglomerate size is influenced by changes in β-sheets and turn conformations. Limitations on study/implications: Effect of pH variation (3.6, 4.6, and 5.6) on morphometric parameters and the secondary structure of proteins (ovalbumin and gliadin). Findings/conclusions: The novelty of this contribution consists in demonstrating that there is a close structure-functionality relationship between the morphometric parameters of proteins and their secondary structure, combining microscopy and spectroscopy techniques. This allows a clear and deep understanding of protein behavior to select the appropriate pH conditions to improve the properties of many foods.

Water stabilizes an alternate turn conformation in horse heart myoglobin

Comparison of myoglobin structures reveals that protein isolated from horse heart consistently adopts an alternate turn conformation in comparison to its homologues. Analysis of hundreds of high-resolution structures discounts crystallization conditions or the surrounding amino acid protein environment as explaining this difference, that is also not captured by the AlphaFold prediction. Rather, a water molecule is identified as stabilizing the conformation in the horse heart structure, which immediately reverts to the whale conformation in molecular dynamics simulations excluding that structural water.

Mutations affect the conformational plasticity of the β2-α2 loop of human prion protein.

The prion protein (PrP) is responsible for several transmissible spongiform encephalopathies such as bovine spongiform encephalopathy and chronic wasting disease in ruminants. In humans, PrP causes Creutzfeldt-Jacob disease, Kuru, and other diseases. The neurotoxicity of PrP manifests upon misfolding and aggregation, and the unfolding of its C-terminal domain is thought to be a key step towards unfolding. PrPs from animals resistant to prion diseases show distinct point mutations in their sequence with respect to human PrP. In this work, we test the hypothesis that the β2-α2 loop in disease-resistant species is characterized by a lower conformational heterogeneity than in human. We test our hypothesis with temperature replica-exchange molecular dynamics and with metadynamics simulations. Our results show that single mutations can alter the equilibrium between the 310-helical turn conformation and several β-turn conformations by reshaping both intra-loop interactions as well as interactions between the loop and the α3-helix.

Naphthyl-Poly(S-((2-carboxyethyl)thio)-l-cysteine) Peptide Amphiphiles with Different Degrees of Polymerization: Synthesis, Self-Assembly, pH/Reduction-Triggered Drug Release, and Cytotoxicity.

Four peptide amphiphiles (PA1-4) with different degrees of polymerization (DP = 40, 15, 10, and 6) were synthesized by Fuchs-Farthing and ring-opening polymerization followed by post-polymerization modification, as fully characterized by 1H NMR, FT-IR, gel permeation chromatography, and circular dichroism (CD) spectroscopy. It was found that PAs could self-assemble to form regular spherical micelles in low-concentration (about 1 mg/mL) aqueous solution, which had different contents of secondary structures and mainly adopted random coil conformations. The water solubility of PAs increases with the increase of DP, the polypeptide chain stretches randomly in water, the β-sheets decrease, and the random coil conformations dominate. When the pH of PA solution decreases or increases, intramolecular hydrogen bonds break, and molecular chains stretch, leading to a decrease of α-helix, turn conformations, and an increase of β-sheets. Meanwhile, the particle size of micelles increases. At around 0.4 mg/mL, the hemolysis ability of PA2 is negligible at pH 7.4 and 6.5 and about 33% at pH 5.5. Cisplatin (CDDP) was linked to micelles by coordination bonds to explore their potential as drug carriers, exhibiting controlled pH and reduction in dual drug release effects. MTT assay showed that the HeLa cell viability was 78% when cultured in the 13.5 μg/mL PA2 blank micelles for 2 days, while the cell viability was 60% in the CDDP-loaded micelles. Furthermore, a high concentration of PA2 (about 100 mg/mL) could self-assemble into a fibrous hydrogel at pH 5.5, which self-healed 2 h after incision and self-degraded 71% within 14 days. The CDDP-loaded fiber hydrogel exhibited a sustained release effect similar to the CDDP-loaded micelles. The cytotoxicity of CDDP-loaded fibers at 48 h was detected to be the same as that of the same amount of CDDP, and the cell viability was 7%. Therefore, we provide a new strategy for the synthesis of amphiphilic peptides with potential applications in nano-drug carriers and cancer therapy.

Structure-activity relationships of mitochondria-targeted tetrapeptide pharmacological compounds

Mitochondria play a central role in metabolic homeostasis, and dysfunction of this organelle underpins the etiology of many heritable and aging-related diseases. Tetrapeptides with alternating cationic and aromatic residues such as SS-31 (elamipretide) show promise as therapeutic compounds for mitochondrial disorders. In this study, we conducted a quantitative structure-activity analysis of three alternative tetrapeptide analogs, benchmarked against SS-31, that differ with respect to aromatic side chain composition and sequence register. We present the first structural models for this class of compounds, obtained with Nuclear Magnetic Resonance (NMR) and molecular dynamics approaches, showing that all analogs except for SS-31 form compact reverse turn conformations in the membrane-bound state. All peptide analogs bound cardiolipin-containing membranes, yet they had significant differences in equilibrium binding behavior and membrane interactions. Notably, analogs had markedly different effects on membrane surface charge, supporting a mechanism in which modulation of membrane electrostatics is a key feature of their mechanism of action. The peptides had no strict requirement for side chain composition or sequence register to permeate cells and target mitochondria in mammalian cell culture assays. All four peptides were pharmacologically active in serum withdrawal cell stress models yet showed significant differences in their abilities to restore mitochondrial membrane potential, preserve ATP content, and promote cell survival. Within our peptide set, the analog containing tryptophan side chains, SPN10, had the strongest impact on most membrane properties and showed greatest efficacy in cell culture studies. Taken together, these results show that side chain composition and register influence the activity of these mitochondria-targeted peptides, helping provide a framework for the rational design of next-generation therapeutics with enhanced potency.

Structural basis of Plasmodium vivax inhibition by antibodies binding to the circumsporozoite protein repeats.

Malaria is a global health burden, with Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) responsible for the majority of infections worldwide. Circumsporozoite protein (CSP) is the most abundant protein on the surface of Plasmodium sporozoites, and antibodies targeting the central repeat region of CSP can prevent parasite infection. Although much has been uncovered about the molecular basis of antibody recognition of the PfCSP repeats, data remains scarce for PvCSP. Here, we performed molecular dynamics simulations for peptides comprising the PvCSP repeats from strains VK210 and VK247 to reveal how the PvCSP central repeats are highly disordered, with minor propensities to adopt turn conformations. Next, we solved eight crystal structures to unveil the interactions of two inhibitory monoclonal antibodies (mAbs), 2F2 and 2E10.E9, with PvCSP repeats. Both antibodies can accommodate subtle sequence variances in the repeat motifs and recognize largely coiled peptide conformations that also contain isolated turns. Our structural studies uncover various degrees of Fab-Fab homotypic interactions upon recognition of the PvCSP central repeats by these two inhibitory mAbs, similar to potent mAbs against PfCSP. These findings augment our understanding of host-Plasmodium interactions and contribute molecular details of Pv inhibition by mAbs to unlock structure-based engineering of PvCSP-based vaccines.

N-Amino-imidazol-2-one (Nai) Residues as Tools for Peptide Mimicry: Synthesis, Conformational Analysis and Biomedical Applications

Abstract N-Amino-imidazol-2-one (Nai) residues are tools for studying peptide-backbone and side-chain conformation and function. Recent methods for substituted Nai residue synthesis, conformational analysis by X-ray crystallography and computation, and biomedical applications are reviewed, demonstrating the utility of this constrained residue to favor biologically active turn conformers with defined χ-dihedral angle orientations.1 Introduction2 Synthetic Methods3 Conformational Analysis4 Biomedical Applications5 Conclusions

Impact of Au144 metal clusters on the structural and inhibitory mechanism of Aβ42 peptide: A theoretical approach

One of the main causes for Alzheimer disease is the abnormal self-assembly of the amyloid-beta (Aβ) peptide, which in turn forms a toxic β-rich aggregation. A recent study suggests that gold nanoparticles (AuNPs) can inhibit the Aβ aggregation. Nevertheless, the effects of AuNPs on Aβ peptide system are still ambiguous and needs exploration that is more detailed. Molecular dynamics simulations have been carried out to investigate the aggregation mechanism of Aβ42 peptide for 500 ns. During simulation, C-terminus regions of Met 35-Ala42 residues exhibits β-sheet conformations. Meanwhile, the Au144MC coordination induces substantial α-helical character, both α-helix and 310-helix structure at 0–500ns, in the region of Asp1-Arg5 and Val36-Ile41 residues. The Au144MC strongly coordinates with Asp1, Ala2, Glu3, Phe4, Asp7, Tyr10 and Gln15 residues that plays the significant effects to loss the β-sheet geometry in the N-terminal region and it converted into random α-helix, turn and bend conformation. On comparing the RMSF of the Aβ42 peptide and Aβ42-Au144MC complex shows that the coordination of Au144MC results in greater rigidity of the Aβ42 peptide backbone regions with exemptions for the Asp1, Ala2, Glu3, Leu34, Ile41 and Ala42 residues due to the strong binding between the metal cluster and the CHC (Leu17−Ala21) region. The structural stability of the Aβ42 peptide and Aβ42-Au144MC complex is enhanced by the several intermolecular and intramolecular interactions and it was visibly revealed in the H-bond. From the above results, it is very evident that the Au144MC can be used as inhibitor agent for the oligomerization of Aβ42.

1,5-Disubstituted 1,2,3-Triazoles as Amide Bond Isosteres Yield Novel Tumor-Targeting Minigastrin Analogs.

1,5-Disubstituted 1,2,3-triazoles (1,5-Tz) are considered bioisosteres of cis-amide bonds. However, their use for enhancing the pharmacological properties of peptides or proteins is not yet well established. Aiming to illustrate their utility, we chose the peptide conjugate [Nle15]MG11 (DOTA-dGlu-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH2) as a model compound since it is known that the cholecystokinin-2 receptor (CCK2R) is able to accommodate turn conformations. Analogs of [Nle15]MG11 incorporating 1,5-Tz in the backbone were synthesized and radiolabeled with lutetium-177, and their pharmacological properties (cell internalization, receptor binding affinity and specificity, plasma stability, and biodistribution) were evaluated and compared with [Nle15]MG11 as well as their previously reported analogs bearing 1,4-disubstituted 1,2,3-triazoles. Our investigations led to the discovery of novel triazole-modified analogs of [Nle15]MG11 with nanomolar CCK2R-binding affinity and 2-fold increased tumor uptake. This study illustrates that substitution of amides by 1,5-disubstituted 1,2,3-triazoles is an effective strategy to enhance the pharmacological properties of biologically active peptides.

Short Arginine-Based Peptides As Predictors for the Extended Structure of Polyarginine Sequences in Intrinsically Disordered Proteins

Intrinsically disordered proteins (IDPs) and regions (IDRs) are often rich with charged amino acids. During important biological processes, protein-biomolecule interactions are often driven by one or more charged residues within an IDR. Several lines of experimental and computational evidence suggest that polypeptides and proteins that carry high net charges tend to adopt extended conformations. Furthermore, the average end to end distances often exceed expectations for self-avoiding random coils. Here, we show that charged arginine (R) residues in even short glycine (G) capped model peptides (GRRG and GRRRG) significantly affect the conformational propensities of each other when compared to the intrinsic propensities of a mostly unperturbed arginine in the tripeptide GRG. A conformational analysis based on experimentally determined J-coupling constants from heteronuclear NMR spectroscopy and amide I’ band profiles from polarized Raman spectroscopy reveals that nearest neighbor interactions stabilize extended β-strand conformations at the expense of polyproline II and turn conformations. The results from MD simulations with an CHARMM36m force field and TIP3P water reproduce our results only to a limited extent. The use of the Ramachandran distribution of the central residue of GRRRG in a calculation of end-to-end distances of polyarginines of different length yielded the expected power law behavior. The scaling coefficient of 0.66 suggests that such peptides would be more extended than predicted by a self-avoiding random walk.

Short peptides as predictors for the structure of polyarginine sequences in disordered proteins

Intrinsically disordered proteins and intrinsically disordered regions are frequently enriched in charged amino acids. Intrinsically disordered regions are regularly involved in important biological processes in which one or more charged residues is the driving force behind a protein-biomolecule interaction. Several lines of experimental and computational evidence suggest that polypeptides and proteins that carry high net charges have a high preference for extended conformations with average end-to-end distances exceeding expectations for self-avoiding random coils. Here, we show that charged arginine residues even in short glycine-capped model peptides (GRRG and GRRRG) significantly affect the conformational propensities of each other when compared with the intrinsic propensities of a mostly unperturbed arginine in the tripeptide GRG. A conformational analysis based on experimentally determined J-coupling constants from heteronuclear NMR spectroscopy and amide I′ band profiles from vibrational spectroscopy reveals that nearest-neighbor interactions stabilize extended β-strand conformations at the expense of polyproline II and turn conformations. The results from molecular dynamics simulations with a CHARMM36m force field and TIP3P water reproduce our results only to a limited extent. The use of the Ramachandran distribution of the central residue of GRRRG in a calculation of end-to-end distances of polyarginines of different length yielded the expected power law behavior. The scaling coefficient of 0.66 suggests that such peptides would be more extended than predicted by a self-avoiding random walk. Our findings thus support in principle theoretical predictions.

Fabrication of porphyrin-based aggregates through modulating hexapeptide secondary conformation

The stacking mode of aggregates directly determines the morphology and properties of assemblies. However, how the peptide secondary confirmation affects the arrangement of artificial photosynthetic supramolecules is still ambiguous. Herein, a porphyrin-hexapeptide supramolecule TPP-Ala-Ala-MV was synthesized to investigate the effect of its secondary conformation on the stacking mode and morphology of aggregates. Nanosheets, nanospheres and nanotubes were obtained from TPP-Ala-Ala-MV at different pH conditions. It was revealed that the pH condition influences not only the aggregation of porphyrin cores, but also its secondary conformation composition. Both experimental and computational results discover that the hexapeptide α-helix conformation has the strongest intramolecular hydrogen bond interaction, whereas no intermolecular hydrogen bond forms in β-sheet conformation. The inclination to J-aggregation, as well as the weak intermolecular interaction among hexapeptide turn conformation, leads to the formation of nanosheets. The inclination to H-aggregation coupled with the strong intermolecular interaction among hexapeptide β-sheet conformations promotes the formation of a highly packed structure, resulting in aggregates of nanosphere or nanotube shape. These results pave the way for the development of artificial photosynthesis systems by regulating the aggregate structures of porphyrin-peptide supramolecular systems.