Molecular self-assembled helix peptide nanotubes based on some amino acid molecules and their dipeptides: molecular modeling studies.

CONTEXT: The paper considers the features of the structure and dipole moments of several amino acids and their dipeptides which play an important role in the formation of the peptide nanotubes based on them. The influence of the features of their chirality (left L and right D) and the alpha-helix conformations of amino acids are taken into account. In particular, amino acids with aromatic rings, such as phenylalanine (Phe/F), and branched-chain amino acids (BCAAs)-leucine (Leu/L) and isoleucine (Ile/I)-as well as corresponding dipeptides (diphenylalanine (FF), dileucine (LL), and diisoleucine (II)) are considered. The main features and properties of these dipeptide structures and peptide nanotubes (PNTs), based on them, are investigated using computational molecular modeling and quantum-chemical semi-empirical calculations. Their polar, piezoelectric, and photoelectronic properties and features are studied in detail. The results of calculations of dipole moments and polarization, as well as piezoelectric coefficients and band gap width, for different types of helical peptide nanotubes are presented. The calculated values of the chirality indices of various nanotubes are given, depending on the chirality of the initial dipeptides-the results obtained are consistent with the law of changes in the type of chirality as the hierarchy of molecular structures becomes more complex. The influence of water molecules in the internal cavity of nanotubes on their physical properties is estimated. A comparison of the results of these calculations by various computational methods with the available experimental data is presented and discussed. METHOD: The main tool for molecular modeling of all studied nanostructures in this work was the HyperChem 8.01 software package. The main approach used here is the Hartree-Fock (HF) self-consistent field (SCF) with various quantum-chemical semi-empirical methods (AM1, PM3, RM1) in the restricted Hartree-Fock (RHF) and in the unrestricted Hartree-Fock (UHF) approximations. Optimization of molecular systems and the search for their optimal geometry is carried out in this work using the Polak-Ribeire algorithm (conjugate gradient method), which determines the optimized geometry at the point of their minimum total energy. For such optimized structures, dipole moments D and electronic energy levels (such as EHOMO and ELUMO), as well as the band gap Eg = ELUMO - EHOMO, were then calculated. For each optimized molecular structure, the volume was calculated using the QSAR program implemented also in the HyperChem software package.

Influence of Magnesium Source on the Mechanochemical Synthesis of Magnesium-Substituted Hydroxyapatite.

Magnesium, as one of the most abundant cations in the human body, plays an important role in both physiological and pathological processes. In this study, it was shown that a promising biomedical material, Mg-substituted hydroxyapatite (Mg-HA), can be synthesized via a fast mechanochemical method. For this method, the nature of magnesium-containing carriers was shown to be important. When using magnesium oxide as a source of magnesium, the partial insertion of magnesium cations into the apatite structure occurs. In contrast, when magnesium hydroxide or monomagnesium phosphate is used, single-phase Mg-HA is formed. Both experimental and theoretical investigations showed that an increase in the Mg content leads to a decrease in the lattice parameters and unit cell volume of Mg-HA. Density functional theory calculations showed the high sensitivity of the lattice parameters to the crystallographic position of the calcium site substituted by magnesium. It was shown experimentally that the insertion of magnesium cations decreases the thermal stability of hydroxyapatite. The thermal decomposition of Mg-HA leads to the formation of a mixture of stoichiometric HA, magnesium oxide, and Mg-substituted tricalcium phosphate phases.

Effect of Magnesium Substitution on Structural Features and Properties of Hydroxyapatite.

Hydroxyapatite (HAP) is the main mineral component of bones and teeth. It is widely used in medicine as a bone filler and coating for implants to promote new bone growth. Ion substitutions into the HAP structure highly affect its properties. One of the most important substituents is magnesium. This paper presents new results obtained using high-precision hybrid density functional theory calculations for Mg/Ca substitutions in HAP in a wide magnesium concentration range within a 2 × 2 × 2 supercell model. Experimental data on the mechanochemical synthesis of HAP-Mg samples with different Mg concentrations are also presented. A comparison between the experiment and the theory showed good agreement: the HAP-Mg unit cell parameters and volume decreased with increasing degree of Mg/Ca substitution. The changes in the distances between the Ca and O, Ca and H, and Mg and O ions upon Mg/Ca substitution in different calcium positions was analyzed. The resulting asymmetry and distortion of the cell parameters were evaluated. It was shown that bulk modulus, energy levels, and band gap depend on the degree of Mg substitutions in the Ca1 and Ca2 positions. The formation energies of Mg/Ca substitutions showed non-monotonic behavior that was different for Ca1 and Ca2 positions. The Ca2 position had a slightly higher probability (~5 meV/f.u.) of substitution than Ca1 position at a Mg concentration x = 0.5. At x = 1, substitution in both positions can coexist. The simulated IR spectra for different Mg/Ca substitutions showed that Mg in the Ca2 position changes the IR spectrum more significantly than Mg in the Ca1 position. Similar changes were recorded in the IR spectra of the synthesized samples. The electronic structure is shown to be sensitive to the number and position of substitutions, which may be used to tweak the optical properties of the HAP-Mg material.

Molecular Dynamics Simulation of Self-Assembly Processes of Diphenylalanine Peptide Nanotubes and Determination of Their Chirality.

In this work, we further developed a new approach for modeling the processes of the self-assembly of complex molecular nanostructures using molecular dynamics methods; in particular, using a molecular dynamics manipulator. Previously, this approach was considered using the example of the self-assembly of a phenylalanine helical nanotube. Now, a new application of the algorithm has been developed for implementing a similar molecular dynamic self-assembly into helical structures of peptide nanotubes (PNTs) based on other peptide molecules-namely diphenylalanine (FF) molecules of different chirality L-FF and D-FF. In this work, helical nanotubes were assembled from linear sequences of FF molecules with these initially different chiralities. The chirality of the obtained nanotubes was calculated by various methods, including calculation by dipole moments. In addition, a statistical analysis of the results obtained was performed. A comparative analysis of the structures of nanotubes was also performed using the method of visual differential analysis. It was found that FF PNTs obtained by the MD self-assembly method form helical nanotubes of different chirality. The regimes that form nanotubes of right chirality D from initial L-FF dipeptides and nanotubes of left chirality L from D-FF dipeptides are revealed. This corresponds to the law of changing the sign of the chirality of molecular helical structures as the level of their hierarchical organization becomes more complicated.

Molecular Dynamics Simulation of the Thermal Behavior of Hydroxyapatite.

Hydroxyapatite (HAP) is the main mineral component of bones and teeth. Due to its biocompatibility, HAP is widely used in medicine as a filler that replaces parts of lost bone and as an implant coating that promotes new bone growth. The modeling and calculations of the structure and properties of HAP showed that various structural defects have a significant effect on the properties of the material. By varying these structural heterogeneities, it is possible to increase the biocompatibility of HAP. An important role here is played by OH group vacancies, which are easily formed when these hydroxyl groups leave OH channels of HAP. In this case, the temperature dependence of the concentration of OH ions, which also determines the thermal behavior of HAP, is important. To study the evaporation of OH ions from HAP structures with increasing temperatures, molecular dynamics simulation (MDS) methods were used in this work. As a program for MDS modeling, we used the PUMA-CUDA software package. The initial structure of HAP, consisting of 4 × 4 × 2 = 32 unit cells of the hexagonal HAP phase, surrounded by a 15-Å layer of water was used in the modelling. Multiple and statistically processed MDS, running calculations in the range of 700-1400 K, showed that active evaporation of OH ions begins at the temperature of 1150 K. The analysis of the obtained results in comparison with those available in the literature data shows that these values are very close to the experiments. Thus, this MDS approach demonstrates its effective applicability and shows good results in the study of the thermal behavior of HAP.

Molecular modelling and computational studies of peptide diphenylalanine nanotubes, containing waters: structural and interactions analysis.

The work is devoted to computer studies of the structural and physical properties of such self-organizing structures as peptide nanotubes (PNT) based on diphenylalanine (FF) dipeptide with different initial isomers of the left (L-FF) and right (D-FF) chiralities of these dipeptides. The structures under study are considered both with empty anhydrous and with internal cavities filled with water molecules. Molecular models of both chiralities are investigated using quantum-chemical DFT and semi-empirical methods, which are in consistent with the known experimental data. To study the effect of nano-sized clusters of water molecules embedded in the inner hydrophilic cavity on the properties of nanotubes (including the changes in their dipole moments and polarizations), as well as the changes in the structure and properties of water clusters themselves (their own dipole moments and polarizations), the surfaces of internal cavities of nanotubes and outer surfaces of water cluster structures for both types of chirality are analyzed. A specially developed method of visual differential analysis of structural features of (bio)macromolecular structures is applied for these studies. The results obtained of a number of physical properties (interacting energies, dipole moments, polarization values) are given for various cases and analyzed in comparison with the known data. These data are necessary for analyzing the interactions of water molecules with hydrophilic parts of nanotube molecules based on FF, such as COO- and NH3 + , since they determine many properties of the structures under study. The data obtained are useful for further analysis of the possible adhesion and capture of medical molecular components by active layers of FF-based PNT, which can be designed for creating capsules for targeted delivery of pharmaceuticals and drugs on their basis.

Molecular Dynamics Simulation Study of the Self-Assembly of Phenylalanine Peptide Nanotubes.

In this paper, we propose and use a new approach for a relatively simple technique for conducting MD simulation (MDS) of various molecular nanostructures, determining the trajectory of the MD run and forming the final structure using external force actions. A molecular dynamics manipulator (MD manipulator) is a controlled MDS type. As an example, the applicability of the developed algorithm for assembling peptide nanotubes (PNT) from linear phenylalanine (F or Phe) chains of different chirality is presented. The most adequate regimes for the formation of nanotubes of right chirality D from the initial L-F and nanotubes of left chirality L of their initial dipeptides D-F modes were determined. We use the method of a mixed (vector-scalar) product of the vectors of the sequence of dipole moments of phenylalanine molecules located along the nanotube helix to calculate the magnitude and sign of chirality of self-assembled helical phenylalanine nanotubes, which shows the validity of the proposed approach. As result, all data obtained correspond to the regularity of the chirality sign change of the molecular structures with a hierarchical complication of their organization.

Quantitative Assessment of Chirality of Protein Secondary Structures and Phenylalanine Peptide Nanotubes.

In this study we consider the features of spatial-structure formation in proteins and their application in bioengineering. Methods for the quantitative assessment of the chirality of regular helical and irregular structures of proteins are presented. The features of self-assembly of phenylalanine (F) into peptide nanotubes (PNT), which form helices of different chirality, are also analyzed. A method is proposed for calculating the magnitude and sign of the chirality of helix-like peptide nanotubes using a sequence of vectors for the dipole moments of individual peptides.

Iron in Hydroxyapatite: Interstitial or Substitution Sites?

Iron-doped hydroxyapatite (Fe-HAp) is regarded as a promising magnetic material with innate biocompatibility. Despite the many studies reported in the literature, a detailed theoretical description of Fe inclusions is still missing. There is even no consensual view on what kind of Fe defects take place in Fe-HAp-iron interstitial or calcium substitutions? In order to address these questions, we employ modern first-principles methodologies, including hybrid density functional theory, to find the geometry, electronic, magnetic and thermodynamic properties of iron impurities in Fe-HAp. We consider a total of 26 defect configurations, including substitutional (phosphorus and calcium sites) and interstitial defects. Formation energies are estimated considering the boundaries of chemical potentials in stable hydroxyapatite. We show that the most probable defect configurations are: Fe3+ and Fe2+ substitutions of Ca(I) and Ca(II) sites under Ca-poor conditions. Conversely, Fe interstitials near the edge of the hydroxyl channel are favored in Ca-rich material. Substitutional Fe on the P site is also a probable defect, and unlike the other forms of Fe, it adopts a low-spin state. The analysis of Fe K-XANES spectra available in the literature shows that Fe-HAp usually contains iron in different configurations.

Simulation and Computer Study of Structures and Physical Properties of Hydroxyapatite with Various Defects.

Simulation and computer studies of the structural and physical properties of hydroxyapatite (HAP) with different defects are presented in this review. HAP is a well-known material that is actively used in various fields of medicine, nanotechnology, and photocatalytic processes. However, all HAP samples have various defects and are still insufficiently studied. First of all, oxygen and OH group vacancies are important defects in HAP, which significantly affect its properties. The properties of HAP are also influenced by various substitutions of atoms in the HAP crystal lattice. The results of calculations by modern density functional theory methods of HAP structures with these different defects, primarily with oxygen and hydroxyl vacancies are analyzed in this review. The results obtained show that during the structural optimization of HAP with various defects, both the parameters of the crystallographic cells of the HAP change and the entire band structure of the HAP changes (changes in the band gap). This affects the electronic, optical, and elastic properties of HAP. The review considers the results of modeling and calculation of HAP containing various defects, the applied calculation methods, and the features of the effect of these defects on the properties of HAP, which is important for many practical applications.

Modeling of Self-Assembled Peptide Nanotubes and Determination of Their Chirality Sign Based on Dipole Moment Calculations.

The chirality quantification is of great importance in structural biology, where the differences in proteins twisting can provide essentially different physiological effects. However, this aspect of the chirality is still poorly studied for helix-like supramolecular structures. In this work, a method for chirality quantification based on the calculation of scalar triple products of dipole moments is suggested. As a model structure, self-assembled nanotubes of diphenylalanine (FF) made of L- and D-enantiomers were considered. The dipole moments of FF molecules were calculated using semi-empirical quantum-chemical method PM3 and the Amber force field method. The obtained results do not depend on the used simulation and calculation method, and show that the D-FF nanotubes are twisted tighter than L-FF. Moreover, the type of chirality of the helix-like nanotube is opposite to that of the initial individual molecule that is in line with the chirality alternation rule general for different levels of hierarchical organization of molecular systems. The proposed method can be applied to study other helix-like supramolecular structures.

Molecular modeling and computational study of the chiral-dependent structures and properties of the self-assembling diphenylalanine peptide nanotubes, containing water molecules.

DFT (VASP) and semi-empirical (HyperChem) calculations for the L- and D-chiral diphenylalanine (L-FF and D-FF) nanotube (PNT) structures, empty and filled with water/ice clusters, are presented and analyzed. The results obtained show that after optimization, the dipole moment and polarization of both chiral type L-FF and D-FF PNT and embedded water/ice cluster are enhanced; the water/ice cluster acquire the helix-like structure similar as L-FF and D-FF PNT. Ferroelectric properties of tubular water/ice helix-like-cluster obtained after optimization inside L-FF and D-FF PNT and total L-FF and D-FF PNT with embedded water/ice cluster are discussed.

Physical Fundamentals of Biomaterials Surface Electrical Functionalization.

This article is focusing on electrical functionalization of biomaterial's surface to enhance its biocompatibility. It is an overview of previously unpublished results from a series of experiments concerning the effects surface electrical functionalization can have on biological systems. Saccharomyces cerevisiae cells were used for biological experiments. The hydroxyapatite (HAp) specimens were used to investigate influence of structural point defects on the surface electrical charge. Threshold photoelectron emission spectroscopy was used to measure the electron work function of HAp and biologic samples. The density functional theory and its different approximations were used for the calculation of HAp structures with defects. It was shown that the electrical charge deposition on the semiconductor or dielectric substrate can be delivered because of production of the point defects in HAp structure. The spatial arrangements of various atoms of the HAp lattice, i.e., PO4 and OH groups, oxygen vacancies, interstitial H atoms, etc., give the instruments to deposit the electrical charge on the substrate. Immobilization of the microorganisms can be achieved on the even surface of the substrate, characterized with a couple of nanometer roughness. This cells attachment can be controlled because of the surface electrical functionalization (deposition of the electrical charge). A protein layer as a shield for the accumulated surface charge was considered, and it was shown that the protein layer having a thickness below 1 µm is not crucial to shield the electrical charge deposited on the substrate surface. Moreover, the influence of surface charge on the attachment of microorganisms, when the surface roughness is excluded, and the influence of controlled surface roughness on the attachment of microorganisms, when surface charge is constant, were also considered.

Structures and Properties of the Self-Assembling Diphenylalanine Peptide Nanotubes Containing Water Molecules: Modeling and Data Analysis.

The structures and properties of the diphenylalanine (FF) peptide nanotubes (PNTs), both L-chiral and D-chiral (L-FF and D-FF) and empty and filled with water/ice clusters, are presented and analyzed. DFT (VASP) and semi-empirical calculations (HyperChem) to study these structural and physical properties of PNTs (including ferroelectric) were used. The results obtained show that after optimization the dipole moment and polarization of both chiral type L-FF and D-FF PNT and embedded water/ice cluster are enhanced; the water/ice cluster acquire the helix-like structure similar as L-FF and D-FF PNT. Ferroelectric properties of tubular water/ice helix-like cluster, obtained after optimization inside L-FF and D-FF PNT, as well of the total L-FF and D-FF PNT with embedded water/ice cluster, are discussed.

Polarization Switching in 2D Nanoscale Ferroelectrics: Computer Simulation and Experimental Data Analysis.

The polarization switching kinetics of nanosized ferroelectric crystals and the transition between homogeneous and domain switching in nanoscale ferroelectric films are considered. Homogeneous switching according to the Ginzburg-Landau-Devonshire (LGD) theory is possible only in two-dimensional (2D) ferroelectrics. The main condition for the applicability of the LGD theory in such systems is its homogeneity along the polarization switching direction. A review is given of the experimental results for two-dimensional (2D) films of a ferroelectric polymer, nanosized barium titanate nanofilms, and hafnium oxide-based films. For ultrathin 2D ferroelectric polymer films, the results are confirmed by first-principle calculations. Fitting of the transition region from homogeneous to domain switching by sigmoidal Boltzmann functions was carried out. Boltzmann function fitting data enabled us to correctly estimate the region sizes of the homogeneous switching in which the LGD theory is valid. These sizes contain several lattice constants or monolayers of a nanosized ferroelectrics.

Molecular modeling and computational study of the chiral-dependent structures and properties of self-assembling diphenylalanine peptide nanotubes.

The structure and properties of diphenylalanine (FF) peptide nanotubes (PNT) based on phenylalanine were investigated by various molecular modeling methods. The main approach employed semi-empirical quantum-chemical methods (PM3 and AM1). Ab initio, density functional theory methods and molecular mechanical approaches were also used. Both model structures and structures extracted from experimental crystallographic databases obtained by X-ray methods were examined. A comparison of optimized model structures and structures obtained by natural self-assembly revealed important differences depending on chirality: D and L. In both the cases, the effect of chirality on the results of self-assembly of FF PNT was established: PNT based on the D-FF has large condensation energy E0 in the transverse direction, and form thicker and shorter PNT bundles than those based on L-FF. A topological difference was established: model PNT were optimized into structures consisting of rings, while naturally self-assembled PNT consisted of helical turns. The latter nanotubes differed from the original L-FF and D-FF and formed helix structures of different chirality signs in accordance with the alternation rule of chirality due to macromolecule hierarchy. A topological transition between ring and helix turn PNT structures is discussed: self-assembled natural helix structures are favorable and their energy is lower by a value of the order of one to several eV.

Effect of the Chloride Anions on the Formation of Self-Assembled Diphenylalanine Peptide Nanotubes.

Self-assembled peptide nanostructures are being intensively investigated due to their potential applications such as biosensors, piezotransducers, and microactuators. It was predicted that their formation and hence piezoelectric property strongly depend on the water content and acidity of the stock solution. In this paper, simple diphenylalanine (FF) tubular structures were fabricated from the solutions with added hydrochloric acid in order to understand the influence of chloride ions on the self-assembly process and resulting piezoelectricity. Low-frequency Raman scattering, atomic, and piezoresponse force microscopies were used to characterize both the morphology and piezoelectric properties of the grown samples. The mechanism of chloride anions' effect on the formation of self-assembled peptide nanostructures is discussed based on the acquired Raman data and quantum-chemical modeling. It is shown that the addition of chloride anions causes a significant reduction of the dipole moments of FF tubes accompanied with the concomitant decrease of tube dimensions and apparent shear piezoelectric coefficients.

Optoelectronics and defect levels in hydroxyapatite by first-principles.

Hydroxyapatite (HAp) is an important component of mammal bones and teeth, being widely used in prosthetic implants. Despite the importance of HAp in medicine, several promising applications involving this material (e.g., in photo-catalysis) depend on how well we understand its fundamental properties. Among the ones that are either unknown or not known accurately, we have the electronic band structure and all that relates to it, including the bandgap width. We employ state-of-the-art methodologies, including density hybrid-functional theory and many-body perturbation theory within the dynamically screened single-particle Green's function approximation, to look at the optoelectronic properties of HAp. These methods are also applied to the calculation of defect levels. We find that the use of a mix of (semi-)local and exact exchange in the exchange-correlation functional brings a drastic improvement to the band structure. Important side effects include improvements in the description of dielectric and optical properties not only involving conduction band (excited) states but also the valence. We find that the highly dispersive conduction band bottom of HAp originates from anti-bonding σ* states along the ⋯OH-OH-⋯ infinite chain, suggesting the formation of a conductive 1D-ice phase. The choice of the exchange-correlation treatment to the calculation of defect levels was also investigated by using the OH-vacancy as a testing model. We find that donor and acceptor transitions obtained within semi-local density functional theory (DFT) differ from those of hybrid-DFT by almost 2 eV. Such a large discrepancy emphasizes the importance of using a high-quality description of the electron-electron interactions in the calculation of electronic and optical transitions of defects in HAp.

HAP nanoparticle and substrate surface electrical potential towards bone cells adhesion: Recent results review.

Nanostructured hydroxyapatite (HAP) and its nanoparticles are widely used for implantation into the human organism. The biocompatibility of the implants depends very much on the interaction between the implant and the cells regenerating tissue to be connected to the implant. An implant surface electrical charged density plays an important role in these processes. Possible instruments managing the surface electrical potential of HAP are in the focus of this paper. Both theoretical and experimental results evidence that: - the surface electrical charge density of the nanoparticle depends on its size and shape; - the electrical charge density of HAP could be engineered by contact less technique because of deposition of the electrical charge from the external radiation source, surface couples reconstruction.

Molecular modeling of the piezoelectric properties of ferroelectric composites containing polyvinylidene fluoride (PVDF) and either graphene or graphene oxide.

Molecular modeling of ferroelectric composites containing polyvinylidene fluoride (PVDF) and either graphene (G) or graphene oxide (GO) were performed using the semi-empirical quantum approximation PM3 in HyperChem. The piezo properties of the composites were analyzed and compared with experimental data obtained for P(VDF-TrFE)-GO films. Qualitative agreement was obtained between the results of the modeling and the experimental results in terms of the properties of the measured effective piezoelectric coefficient d 33eff and its decrease in the presence of G/GO in comparison with the average computed piezoelectric coefficient . When models incorporating one or several G layers with 54 carbon atoms were investigated, the average piezoelectric coefficient was found to decrease to -9.8 pm/V for the one-sided model PVDF/G and to -18.98 pm/V for the sandwich model G/PVDF/G as compared with the calculated piezoelectric coefficient for pure PVDF ( = -42.2 pm/V computed in present work, and = -38.5 pm/V, obtained from J Mol Model 35 (2013) 19:3591-3602). When models incorporating one or several GO layers with 98 carbon atoms were considered, the piezoelectric coefficient was found to decrease to -14.6 pm/V for the one-sided PVDF/GO model and to -29.8 pm/V for the sandwich GO/PVDF/GO model as compared with the same calculated piezoelectric coefficient for pure PVDF.