Conformational Profile Research Articles

High-efficiency X-ray multilayer-coated blazed gratings with shifted boundaries.

A new design for a high-efficiency multilayer-coated blazed X-ray grating with horizontal-shifted (non-conformal) boundary profiles is proposed. The investigation of the grating design is carried out using an integrated approach based on rigorous numerical calculations of light diffraction by gratings with realistic boundary profiles obtained from simulations of multilayer grating growth. By varying the incidence angle of the deposition flux, one can set the direction and magnitude of the boundary profile shifts over a wide range of values. It is shown that the diffraction efficiency of the blazed gratings with shifted boundary profiles may be substantially higher than the efficiency of gratings with conformal boundaries, which are, moreover, much more difficult to produce. High-efficiency gratings with shifted boundaries can be obtained when the deposition is mainly on the blaze facet with a high inclination of the deposition flux, as opposed to widely used near-normal deposition methods. The maximum absolute efficiency of a W/B4C 2500 mm-1 grating with a blaze angle of 1.76° and an anti-blaze angle of 20°, working at a blaze wavelength of 1.3 nm and having shifted realistic boundary profiles, obtained using our integrated approach is 23.3%, while that of a grating with the ideal (triangular) boundary profile and the same shifts is 25.3%, and that of an ideal conformal profile is only 22.2%. The maximum absolute efficiency of 40.2% of a 2500 mm Cr/C grating with a blaze angle of 1.05° and a realistic anti-blaze angle of 10°, working at a blaze wavelength of 0.83 nm and having ideal shifted boundaries, is higher than the maximum efficiency of the similar grating having ideal conformal boundaries with a non-realistic anti-blaze angle of 80°.

Dissociation of β-Arrestin-Dependent Desensitization and Signaling Using 'Biased' Parathyroid Hormone Receptor Ligands

While structurally distinct ligands can “bias” the efficiency with which G protein-coupled receptors (GPCRs) activate different downstream effectors, it is thought that the events downstream of a single effector are inseparable. We tested a panel of type 1 parathyroid hormone receptor (PTH1R) ligands for their effects on two β-arrestin-mediated processes, receptor desensitization and β-arrestin-dependent signaling. Unlike conventional agonists, which caused desensitization while activating β-arrestin-dependent signaling, we found that β-arrestin biased agonists that did not activate G protein signaling or desensitize the receptor paradoxically retained the ability to signal via β-arrestins. Total internal fluorescence microscopy, bimolecular fluorescent complementation between PTH1R and β-arrestin2, and intramolecular β-arrestin2 FlAsH-BRET conformational profiling demonstrated that these ligands transiently recruit β-arrestin2 to the receptor and induced distinctive changes in β-arrestin2 conformation without a requirement for stable binding. Our results demonstrate that β-arrestin-dependent signaling can be dissociated from receptor desensitization and establish a novel profile of β-arrestin-dependent efficacy.

Determination of Dimension and Conformal Arsenic Doping Profile of a Fin Field Effect Transistors by Time-of-Flight Medium Energy Ion Scattering.

We have developed a methodology that analyzes the dimensions and conformal doping profiles in fin field effect transistors (FinFET) using time-of-flight medium energy ion scattering (TOF-MEIS). The structure of a 3D FinFET and As dopant profiles were determined by comprehensive simulations of TOF-MEIS measurements made in three different scattering geometries. The width and height of a FinFET and the As doping profiles in the top, side, and bottom of fin were analyzed simultaneously. The results showed the dimension and conformal doping profile of nanostructures with complex shape can be determined by TOF-MEIS nondestructively, quantitatively, and with subnm depth resolution without any sputtering and matrix effects.

Endomorphin-2 analogs containing modified tyrosines: Biological and theoretical investigation of the influence on conformation and pharmacological profile

New analogs of the endogenous opioid agonist endomorphin-2 (EM-2, H-Tyr-Pro-Phe-Phe-NH2) have been obtained by introducing modified tyrosines at the position 1 of the sequence. For all analogs, the cis/trans conformation ratio about the tyramine-Pro amide bond, lipophilicity, receptor affinities, and functional activities, have been determined. Among the novel derivatives, [Dmt(3′-Cl)]1EM-2 (4) stood out for its subnanomolar μ-opioid receptor affinity and potent agonist activity, superior to that of the parent peptide EM-2. Hybrid quantum mechanics/molecular mechanics docking computations supported the cis tyramine-Pro bioactive conformation, and allowed us to analyze the contribution of the substituents of the “message” tyramine to binding, highlighting the role of halogen-bonding in the higher receptor affinity of peptide 4.

Conformational profile, vibrational assignments, NLO properties and molecular docking of biologically active herbicide1,1-dimethyl-3-phenylurea

1,1-Dimethyl-3-phenylurea (known as fenuron) which is a phenyl urea-based widely used herbicide exhibits interesting structural and conformational properties and a notable biological activity. A detailed analysis on the vibrational, molecular and electronic characteristics of fenuron has been carried out. Potential energy scans (PESs) performed at the B3LYP/6-311++G(d,p) level of theory predicted two possible minima corresponding to the optimized anti and synforms resulting from the internal rotation about the N-C bond. The presence of an auxochrome together with the interaction with DMSO solvent exhibited a blue shift corresponding to the C=O orbitals. Delocalization of HOMO and LUMO orbital facilitated the charge transfer effect in the molecule. The calculated HOMO-LUMO energies, chemical potential, energy gap and global hardness suggested a low softness value for the compound while its biological activity was described by the value of electrophilicity. Chlorine substitution in the phenyl ring influenced the orbital delocalization for ortho and para substitutions but that of meta remained unaffected. NLO properties were noticed to increase due to chlorine substitution in the parent molecule. The docking results suggested that the compound exhibits an inhibitory activity against mitochondrial ubiquinol-cytochrome-c reductase and can be developed as a potential anticancer agent.

SAT-033 Studying Cell-Context Specific Effects on the Function of the AT1R in iPSCs and Their Differentiated Derivatives

Cardiovascular homeostasis is tightly regulated by numerous neurohormonal mediators such as the renin-angiotensin system which plays an important role in the maintenance of blood pressure. Central to this system is the peptide hormone angiotensin II (Ang II) whose signals are transduced via the AT1 receptor (AT1R), an important member of the superfamily of G protein-coupled receptors (GPCRs). Ang II binding results in receptor activation characterized by structural re-arrangements within the receptor structure and the subsequent activation of its cognate G protein partners. GPCRs are allosteric in nature and their biological activity is highly dependent on the cell context in which they are expressed1. Changes in the cellular background such as the differential availability of G proteins and effector molecules including putative dimer partners can affect receptor conformation and function. As such, we are interested in understanding how AT1R conformation and signaling are modulated by the cell context in which it is expressed1. In the past, studies that aimed at understanding signaling downstream of GPCRs mostly relied on heterologous expression systems such as HEK 293 cells because of their ease of culture. Such studies led to a ‘one size fits all’ notion that our findings could be reasonably extrapolated to guide drug discovery platforms relevant for human disease. However, it is clear that with the high rate of drug attrition, we need more physiologically relevant cellular models for studies of molecular signal transduction events to be translatable. With this in mind, we are generating iPSCs that stably express a panel of conformation-sensitive biosensors that reliably report on the conformational changes in the AT1R1,2. Our biosensors use resonance energy transfer between a bioluminescent donor and a fluorescent acceptor (FlAsH) where agonist-mediated conformational changes can be recorded1. Here, we will investigate how the conformation of the AT1R changes when expressed in AT1R-relevant cell types such as iPSC-derived cardiomyocytes and vascular smooth muscle cells. We will investigate how our conformational profiles differ in different iPSC-derived cell types in response to AT1R-specific agonists. Our goal is to gain a better mechanistic understanding of how cells are differentially wired leading to cell-specific conformational and signaling responses. We hope our results can guide rational drug design to better target the AT1R and other GPCRs. 1Devost D., et al (2017). Journal of Biological Chemistry, jbc-M116. 2Pei Y., et al (2015). Scientific reports, 5, 9205.

Improved enzymatic accessibility of peanut protein isolate pre-treated using thermosonication

Thermosonication pre-treatment was used to enhance the pancreatin-induced proteolysis of peanut protein isolate (PPI). Response surface methodology was applied to optimize the thermosonication conditions (including power-output and temperature), and the highest degree of hydrolysis (7.16%) was obtained at 475.0 W, 72 °C. SDS-PAGE analysis showed that at this optimized condition, the enzymatic accessibility of the major constitutive protein arachin in thermosonicated PPI (TS-PPI) was substantially improved compared to that in untreated PPI or sonicated PPI (475 W, 30 °C; S-PPI), resulting in a remarkable increase in protein solubility for the hydrolysates. Protein denaturation and conformation profiles of untreated PPI, S-PPI and TS-PPI were investigated using differential scanning calorimetry, intrinsic fluorescence emission spectroscopy, Fourier transform infra-red spectroscopy and thioflavin-T (ThT) fluorescence assay. It was found that heat could present a markedly additive effect to ultrasound on denaturing peanut proteins, leading to significant changes in protein conformation. TS-PPI was characterized by the appearance of high proportion of parallel intermolecular β-sheets and a strong fluorescence enhancement upon binding to ThT, suggesting that the protein unfolding and aggregation induced by thermosonication probably resulted in the formation of fibril protein aggregates in TS-PPI rather than spherical protein aggregates formed in S-PPI. As a result, the protein conformation of TS-PPI appeared to be more unfolded and flexible than that of untreated PPI or S-PPI, and therefore was more easily accessible to protease. This study shows that thermosonication pre-treatment could be a highly effective and feasible technique to improve the enzymatic accessibility of globular proteins, producing prominent functional benefits for the protein hydrolysates.

4D-QSAR studies of CB2 cannabinoid receptor inverse agonists: a comparison to 3D-QSAR

Over the years QSAR methods have developed from 2D-QSAR to more complex 4D-QSAR which features freedom of alignment and conformational flexibility of individual ligands. This approach takes advantage of conformational ensemble profile (CEP) generated for individual compounds by molecular dynamics simulations. In present study, the 4D-QSAR methods called LQTAgrid-QSAR has been performed on a series of potent CB2 cannabinoid receptor inverse agonists. Step-wise method was used to select the most informative variables. Partial least squares (PLS) and multiple linear regression (MLR) methods were used for constructing the regression models. Y-randomization and leave-N-out cross-validation (LNO) were carried out to verify the robustness of the model and to analysis of the independent test set. Best 4D-QSAR model provided the following statistics: R2 = 0.862, q2LOO = 0.737, q2LNO = 0.719, R2Pred = 0.884 (PLS) and R2 = 0.863, q2LOO = 0.771, q2LNO = 0.761, R2Pred = 0.877 (MLR). The comparison of the 4D-QSAR to 3D-QSAR was performed.

Dynamics of an isolated railway wheelset with conformal wheel–rail interactions

ABSTRACTIn multi-body dynamics, we model a non-conformal wheel/rail contact at one centre point since this contact is flat and Hertzian. However, the quasi-conformal contact requires more points since the contact is curved and non-Hertzian. The methodology in solving these points during dynamic simulations is the basis of this development. In this online effort, first, we present a general contact joint and the gutter search method of Pascal and Jourdan [The rigid-multi-Hertzian method as applied to conformal contacts. USA: ASME; 2007] in the context of a multi-body approach. Next, by adopting the non-iterative approach, a subset of these points with positive profile interpenetrations is selected to idealise one curved contact by a set of multi-Hertzian patches for which the Hertz normal contact solution is available. Finally, the feasibility of this multibody approach together with its implementation in two different codes is evaluated by simulating the motion of an isolated wheelset with realistic inertia. On tangent tracks, the wheelset with non-conformal pairing displays self-excited unstable oscillations while it displays a stable behaviour below a critical speed with conformal profiles. A further study reveals the net friction losses at multiple patches within the curved contact being the reason for the stable behavior.

Biased Agonist TRV027 Determinants in AT1R by Molecular Dynamics Simulations.

Functional selectivity is a phenomenon observed in G protein-coupled receptors in which intermediate active-state conformations are stabilized by mutations or ligand binding, resulting in different sets of signaling pathways. Peptides capable of selectively activating β-arrestin, known as biased agonists, have already been characterized in vivo and could correspond to a new therapeutic approach for treatment of cardiovascular diseases. Despite the potential of biased agonism, the mechanism involved in selective signaling remains unclear. In this work, molecular dynamics simulations were employed to compare the conformational profile of the angiotensin II type 1 receptor (AT1R) crystal bound to angiotensin II, bound to the biased ligand TRV027, and in the apo form. Our results show that both ligands induce changes near the NPxxY motif in transmembrane domain 7 that are related to receptor activation. However, the biased ligand does not cause the rotamer toggle alternative positioning and displays an exclusive hydrogen-bonding pattern. Our work sheds light on the biased agonism mechanism and will help in the future design of novel biased agonists for AT1R.

Combining Conformational Profiling of GPCRs with CRISPR/Cas9 Gene Editing Approaches.

Ligand-biased signaling could have a significant impact on drug discovery programs. As such, many approaches to screening now target a larger section of the signaling responses downstream of an individual G protein-coupled receptor (GPCR). Biosensor-based platforms have been developed to capture signaling signatures. Despite the ability to use such signaling signatures, they may still be particular to an individual cell type and thus such platforms may not be portable from cell to cell, necessitating further cell-specific biosensor development. We have developed a complementary strategy based on capturing receptor-proximal conformational profiles using intra-molecular BRET-based sensors composed of a Renilla luciferase donor engineered into the carboxy-terminus and CCPGCC motifs which bind fluorescent hairpin biarsenical dyes engineered into different positions into the receptor primary structure. Here, we discuss how these experiments can be conducted and combined with CRISPR/Cas9 genome editing to assess specific G protein-dependent and -independent events.

Physicochemical property based computational scheme for classifying DNA sequence elements of Saccharomyces cerevisiae

GenerationE of huge “omics” data necessitates the development and application of computational methods to annotate the data in terms of biological features. In the context of DNA sequence, it is important to unravel the hidden physicochemical signatures. For this purpose, we have considered various sequence elements such as promoter, ACS, LTRs, telomere, and retrotransposon of the model organism Saccharomyces cerevisiae. Contributions due to di-nucleotides play a major role in studying the DNA conformation profile. The physicochemical parameters used are hydrogen bonding energy, stacking energy and solvation energy per base pair. Our computational study shows that all sequence elements in this study have distinctive physicochemical signatures and the same can be exploited for prediction experiments. The order that we see in a DNA sequence is dictated by biological regions and hence, there exists role of dependency in the sequence makeup, keeping this in mind we are proposing two computational schemes (a) using a windowing block size procedure and (b) using di-nucleotide transitions. We obtained better discriminating profile when we analyzed the sequence data in windowing manner. In the second novel approach, we introduced the di-nucleotide transition probability matrix (DTPM) to study the hidden layer of information embedded in the sequences. DTPM has been used as weights for scanning and predictions. This proposed computational scheme incorporates the memory property which is more realistic to study the physicochemical properties embedded in DNA sequences. Our analysis shows that the DTPM scheme performs better than the existing method in this applied region. Characterization of these elements will be a key to genome editing applications and advanced machine learning approaches may also require such distinctive profiles as useful input features.

Combining Optical Approaches with Human Inducible Pluripotent Stem Cells in G Protein-Coupled Receptor Drug Screening and Development.

Drug discovery for G protein-coupled receptors (GPCRs) stands at an interesting juncture. Screening programs are slowly moving away from model heterologous cell systems such as human embryonic kidney (HEK) 293 cells to more relevant cellular, tissue and whole animal platforms. Investigators are now developing analytical approaches as means to undertake different aspects of drug discovery by scaling into increasingly more relevant models all the way down to the single cell level. Such approaches include cellular, tissue slice and whole animal models where biosensors that track signaling events and receptor conformational profiles can be used. Here, we review aspects of biosensor-based imaging approaches that might be used in inducible pluripotent stem cell (iPSC) and organoid models, and focus on how such models must be characterized in order to apply them in drug screening.

Effects of the N, O, and S heteroatoms on the adsorption and desorption of asphaltenes on silica surface: A molecular dynamics simulation

The adsorption and desorption of asphaltene on silica surface is highly dependent on the heteroatoms present in its structure. Herein, some model asphaltene molecules with different heteroatoms (i.e., N, O, S) at different positions (in the aromatic cores, in the middle and termination of alkane side chains) are selected as the adsorbates to investigate their adsorption and desorption behaviors on silica surface through molecular dynamics (MD) simulation. Results reveal that the characteristic adsorption configuration of asphaltenes is ascribed to the competition between the asphaltene-silica interaction and π–π stacking interaction among the asphaltene polyaromatic rings. The presence of heteroatoms is found to be able to strengthen the interactions between asphaltenes and silica, depending on their type and location. For example, the terminal polar groups, especially the carboxyl (COOH), exhibit the greatest contribution to the electrostatic interaction (increasing from −81 to −727 kJ/mol). The S atoms are also found to increase the van der Waals interaction energies by 25%. According to the equilibrium desorption conformation and density profile, the presence of heteroatoms is found to significantly hinder the desorption of asphaltenes from silica due to the enhanced polar interactions. The impeded desorption is also confirmed by the slower detachment of asphaltenes based on the time-dependent interaction energies and center of mass (COM) distances analysis. Additionally, the terminal polar groups lead to extraordinary desorption properties of asphaltenes. It is observed that the strong asphaltene-silica and asphaltene-water interactions coexist in these systems due to the high polarity and hydrophilicity of the terminal polar groups.

Quantitative conformational profiling of kinase inhibitors reveals origins of selectivity for Aurora kinase activation states

Protein kinases undergo large-scale structural changes that tightly regulate function and control recognition by small-molecule inhibitors. Methods for quantifying the conformational effects of inhibitors and linking them to an understanding of selectivity patterns have long been elusive. We have developed an ultrafast time-resolved fluorescence methodology that tracks structural movements of the kinase activation loop in solution with angstrom-level precision, and can resolve multiple structural states and quantify conformational shifts between states. Profiling a panel of clinically relevant Aurora kinase inhibitors against the mitotic kinase Aurora A revealed a wide range of conformational preferences, with all inhibitors promoting either the active DFG-in state or the inactive DFG-out state, but to widely differing extents. Remarkably, these conformational preferences explain broad patterns of inhibitor selectivity across different activation states of Aurora A, with DFG-out inhibitors preferentially binding Aurora A activated by phosphorylation on the activation loop, which dynamically samples the DFG-out state, and DFG-in inhibitors binding preferentially to Aurora A constrained in the DFG-in state by its allosteric activator Tpx2. The results suggest that many inhibitors currently in clinical development may be capable of differentiating between Aurora A signaling pathways implicated in normal mitotic control and in melanoma, neuroblastoma, and prostate cancer. The technology is applicable to a wide range of clinically important kinases and could provide a wealth of valuable structure-activity information for the development of inhibitors that exploit differences in conformational dynamics to achieve enhanced selectivity.

A Dosimetric Analysis of Dorsal Nerve Root Ablation Therapy using a Virtual Cone Technique

Virtual cone radiosurgery has been established as an effective treatment for trigeminal neuralgia. This delivery technique employs multiple static-field arcs with HDMLC-defined apertures to deliver high doses to small target volumes (<1cc) with sharp dose gradients. As a replacement to a physical cone, virtual cone delivery has the advantage of reduced treatment times and superior intra-fractional motion monitoring capability, while eliminating the need for Co-60 radiosurgery units. There is currently clinical interest in employing virtual cone techniques in the ablation of dorsal nerve root ganglia as a treatment for chronic thoraco-abdominal pain. We hypothesize that a standard template for single-fraction virtual cone treatment may be established to achieve ablative 90Gy point doses to the ganglia while adhering to conventional OAR dose constraints. This would enable the first such application of virtual cone treatment outside of cranial cases. Dosimetric analysis of virtual cone plans was performed within our institution’s treatment planning system using a linear Boltzman transport equation model on a 1mm grid. 10MV flattening filter-free beams were used at a 2400 MU/minute dose rate. Calculation accuracy was assessed using orthogonal film measurements in an anatomical phantom. Film-based verification indicated that dose discrepancies relative to the calculation model were <4%. Having established the accuracy of our calculations, various arc arrangements, HDMLC-defined field sizes, and collimator angles were investigated. The optimal field arrangement involved 10 equally weighted arcs at 0, ±7.5, and ±15 degree couch angles. For left-nerve root treatment, arcs ran from 10-170 degrees, with a 60-120 degree skip arc (with mirrored arcs for right-nerve root treatment). Delivery time was 25 minutes. The four innermost HDMLC leaves formed a 10mm x 4mm aperture, with jaws at 11mm x 5mm. ±5 degree collimator angles were used in repeated arcs. Doses were normalized to a 90Gy point dose at the target center. In both a thorax phantom and a test patient plan, this arrangement produced a 60Gy isodose surface approximately 5.5mm x 7.5mm x 7.5mm along the lateral, A-P, and S-I axes, respectively. The maximum dose to the spinal cord was 4.14Gy, and the maximum dose to the esophagus was 12.08Gy, with a V12 of <0.001cc. Results of this dosimetric study indicate that ablative doses can be delivered to dorsal nerve root ganglia while respecting normal tissue constrains. Furthermore, due to the robustly conformal dose profile achieved and the elimination of inverse-planning, it is probable that this virtual cone technique can be safely employed as a standardized template treatment for most patients (subject to dose constraint verification), eliminating the need for time-consuming optimization and allow for the expedited treatment of patients with intractable pain.

Sistem Pendukung Keputusan Kelompok Pemilihan e-commerce/marketplace menggunakan metode profile matching dan BORDA

The increasing development of information technology, brings developments to the pattern of life of the Indonesian people, especially the pattern of consumption and shipping of goods. Indonesian society is greatly facilitated and spoiled in getting the desired goods and services. This development was caused by the spread of online shopping providers in Indonesia, which can be accessed via smartphones and computers. Indonesia has a very high number of smartphone users, judging from the number of unique audiences at the end of the second quarter, the data obtained from MMX Multi-platform, June 2017. One of the models used in this study is the Profile Matching method, the method can overcome problems ranking by giving weights based on matching two profiles examined on the criteria of each cell phone. The criteria obtained by the user will be the profile value which is then matched with the conformity profile provided by DM. This study uses three decision makers, including economists, IT experts, and the public. To combine the three decisions used the BORDA method approach. The BORDA method is a voting method that can resolve group decision making, wherein its application each decision maker (DM) provides a rating based on the alternative choices available. Furthermore, this research will use the approach of profile matching and BORDA methods in choosing the best marketplace. The results showed that Sophie's marketplace was ranked first.

Conformational equilibrium study of calix[4]tetrolarenes using Density Functional Theory (DFT) and Molecular Dynamics simulations

ABSTRACTThe present work deals with the theoretical study of conformational equilibrium of calix[4]tetrolarenes (1,2,3 trimethoxy substituted calix[4]arene) in gaseous and solvation phases. A total of 64 calculations (four conformations at eight level of theories) were performed using Density Functional Theory (DFT) functionals viz. wB97XD, B97D, B3LYP, CAM-B3LYP with diffused (6–31 + G(d)) and non-diffused basis sets (6-31G(d)). It has been found that the conformational profile of calix[4]tetrolarene changes from cone to 1,3-Alternate upon incorporating – OMe group. The B97D and wB97XD functionals gave the most accurate result having rmsd value ~0.73Å followed by B3LYP and CAM-B3LYP > 0.78Å. Furthermore, NBO calculations demonstrated that reduction in charges at lower rim oxygens reduces the chances of hydrogen bonding. Moreover, global reactivity parameters and molecular dynamics also complement the observed trend. Owing to the methoxy substitutions, anion binding study of these new molecules indicates towards the promising capability to bind Cl− and F− ions.

The Electron-Conformational Model of Ryanodine Receptors of the Heart Cell

The main ideas of an electron-conformational (EC) model of ligand-activated ryanodine channels (RyR) that reduces many degrees of freedom of this gigantic nanoscopic molecular complex to two so-called electron and conformational degrees of freedom are presented. In the toy model, the conformational potential or energy profile of the RyR channel represents two branches that describe the dependence of energy on the conformational coordinate (reaction coordinate) in the initial and ligand-activated states, respectively. A model extension that takes into account both the tetrameric structure of the RyR channel and additional (orthogonal) rotational conformational mode has been considered. The EC model has been demonstrated to give a biophysical basis to the traditional phenomenological model of Markov chains. To demonstrate the possibilities of the EC model, we refer to examples of model description of the dynamics of isolated RyR channels and clusters of RyR channels in release units of the heart cell.

Conformational Conversion during Controlled Oligomerization into Nonamylogenic Protein Nanoparticles.

Protein materials are rapidly gaining interest in materials sciences and nanomedicine because of their intrinsic biocompatibility and full biodegradability. The controlled construction of supramolecular entities relies on the controlled oligomerization of individual polypeptides, achievable through different strategies. Because of the potential toxicity of amyloids, those based on alternative molecular organizations are particularly appealing, but the structural bases on nonamylogenic oligomerization remain poorly studied. We have applied spectrofluorimetry and spectropolarimetry to identify the conformational conversion during the oligomerization of His-tagged cationic stretches into regular nanoparticles ranging around 11 nm, useful for tumor-targeted drug delivery. We demonstrate that the novel conformation acquired by the proteins, as building blocks of these supramolecular assemblies, shows different extents of compactness and results in a beta structure enrichment that enhances their structural stability. The conformational profiling presented here offers clear clues for understanding and tailoring the process of nanoparticle formation through the use of cationic and histidine rich stretches in the context of protein materials usable in advanced nanomedical strategies.