Effect of ionized protein residues on the nucleation pathway of protein folding

Using a ternary nucleation formalism, we have recently [Y. S. Djikaev and E. Ruckenstein, J. Chem. Phys. 126, 175103 (2007)] proposed a kinetic model for the nucleation mechanism of protein folding. A protein was considered as a heteropolymer consisting of hydrophobic, hydrophilic, and neutral beads with all the bonds having the same constant length and all the bond angles equal and fixed. In this paper, we further develop that model by taking into account of the ionizability of some of the protein residues. As previously, an overall potential around the cluster wherein a protein residue performs a chaotic motion is considered to be a combination of the average dihedral and average pairwise potentials (the latter now including an electrostatic contribution for ionized residues) assigned to the residue and the confining potential due to the polymer connectivity constraint. The overall potential as a function of the distance from the cluster has a double well shape (even for ionized beads) which allows one to determine the rates of emission and absorption of residues by the cluster by using a first passage time analysis. Assuming the equality of the ratios of the numbers of negatively and positively ionized residues in the cluster and in the entire protein, one can keep the modified model within the framework of the ternary nucleation formalism and evaluate the size and composition of the nucleus and the protein folding time as in the previous model. As an illustration, the model is again applied to the folding of bovine pancreatic ribonuclease consisting of 124 amino acids, whereof 40 are hydrophobic, 81 hydrophilic (of which 10 are negatively and 18 positively ionizable), and 3 neutral. Numerical calculations at pH=6.3, pH=7.3, and pH=8.3 show that for this protein the time of folding via nucleation is significantly affected by electrostatic interactions only for the unusually low pH of 6.3 and that among all pH's considered pH=7.3 provides the lowest folding time.     

Eigenvalues of ‐Free Graphs and the Connectivity of Their Independence Complexes

Let G be a graph on n vertices, with maximal degree d, and not containing as an induced subgraph. We prove:

• 1.
• 2.

Here is the maximal eigenvalue of the Laplacian of G, is the independence complex of G, and denotes the topological connectivity of a complex plus 2. These results provide improved bounds for the existence of independent transversals in ‐free graphs.     

Effect of fluid-solid interactions on symmetry breaking in closed nanoslits

The possibility of symmetry breaking of the fluid (argon) density distribution across a long closed slit with identical walls composed of solid carbon dioxide was noted in previous papers by the authors. The main conclusion was that there is a range of average densities in which symmetry breaking occurs and that outside that range the fluid density profile is symmetrical. A critical temperature T(sb) was also identified below which symmetry breaking can occur. In this paper, symmetry breaking is examined for walls made of other materials and it is shown that it occurs only when the energy parameter epsilon(fw) of the fluid-wall interaction in the Lennard-Jones potential satisfies the inequalities epsilon(fw1) < or = epsilon(fw) < or = epsilon(fw2), where epsilon(fw1) and epsilon(fw2) are temperature-dependent critical values of epsilon(fw). The value of epsilon(fw1) increases and that of epsilon(fw2) decreases with increasing temperature. The comparison of the theory with Monte Carlo simulations confirms the existence of symmetry breaking across the slit. The possibility of symmetry breaking along the slit is also noted.     

Cooperativity in ordinary ice and breaking of hydrogen bonds

The total interaction energy between two H-bonded water molecules in a condensed phase is composed of a binding energy between them and an energy due to a cooperative effect. An approximate simple expression is suggested for the dependence of the interaction energy between two H-bonded water molecules on the number of neighboring water molecules with which they are H-bonded. Using this expression, the probabilities of breaking a H bond with various numbers of H-bonded neighbors are estimated. These probabilities are used in computer simulations of the breaking of specified fractions of H bonds in an ordinary (hexagonal) ice. A large "piece" of hexagonal ice (up to 8 millions molecules) is built up, and various percentages of H bonds are considered broken. It is shown that 62-63% of H bonds must be broken in order to disintegrate the "piece" of ice into disconnected clusters. This value is only a little larger than the percolation threshold (61%) predicted both by the percolation theory for tetrahedral ice and by simulations in which all H bonds were considered equally probable to be broken. When the percentage of broken bonds is smaller than 62-63%, there is a network of H-bonded molecules which contains the overwhelming majority of water molecules. This result contradicts some models of water which consider that water consists of a mixture of water clusters of various sizes. The distribution of water molecules with unequal probabilities for breaking is compared with the simulation involving equal probabilities for breaking. It was found that in the former case, there is an enhanced number of water monomers without H bonds, that the numbers of 2- and 3-bonded molecules are smaller, and the number of 4-bonded molecules is larger than in the latter case.     

Colored-descent representations of complex reflection groups <Emphasis Type="Italic">G</Emphasis>(<Emphasis Type="Italic">r,p, n</Emphasis>)

We study the complex reflection groups G(r, p, n). By considering these groups as subgroups of the wreath products , and by using Clifford theory, we define combinatorial parameters and descent representations of G(r, p, n), previously known for classical Weyl groups. One of these parameters is the flag major index, which also has an important role in the decomposition of these representations into irreducibles. A Carlitz type identity relating the combinatorial parameters with the degrees of the group, is presented.     

Independent systems of representatives in weighted graphs

The following conjecture may have never been explicitly stated, but seems to have been floating around: if the vertex set of a graph with maximal degree Δ is partitioned into sets V _i of size 2Δ, then there exists a coloring of the graph by 2Δ colors, where each color class meets each V _i at precisely one vertex. We shall name it the strong 2Δ-colorability conjecture. We prove a fractional version of this conjecture. For this purpose, we prove a weighted generalization of a theorem of Haxell, on independent systems of representatives (ISR’s). En route, we give a survey of some recent developments in the theory of ISR’s. The research of the first author was supported by grant no 780/04 from the Israel Science Foundation, and grants from the M. & M. L. Bank Mathematics Research Fund and the fund for the promotion of research at the Technion. The research of the third author was supported by the Sacta-Rashi Foundation.     

Multicomponent polymer coating to block photocatalytic activity of TiO2 nanoparticles

Chemical grafting of anti-oxidant molecules with an additional hydrophobic polymer coating directly onto TiO(2) particle surfaces, using sonochemistry, is found to eliminate photocatalytic degradation enabling highly effective screening against UV radiation.     

Self-assembling of ABC linear triblock copolymers in nanocylindrical tubes

By employing Monte Carlo simulations for various tube diameters and preferences of the tube surface for the A, B, and C segments, the morphologies of A(5)B(5)C(5), A(5)B(10)C(5), and A(5)B(5)C(10) triblock copolymer melts confined in nanocylindrical tubes were examined. The interaction parameters between different segments were considered constant epsilon(AB)=epsilon(AC)=epsilon(BC)=0.3k(B)T, the tube diameter was changed from d=9xlattice parameter to d=33xlattice parameter, and the preferences of the tube surface for the segments A, B, and C (-epsilon(AS),-epsilon(BS), and -epsilon(CS)) were varied between 0.05k(B)T and k(B)T. ABCCBA alternately stacked disks were generated in most tubes when the preference of the tube surface for any of the segments was weak, and the morphologies tended to transform into curved lamellae in tubes with large diameters when the preference for one of the segments was high. Numerous novel morphologies, such as ABC double helixes, AB single helix+C double helixes, AB double helixes+C quadruple helixes, plate morphologies with fins, dendrites, etc., which were located in the phase diagram between the stacked disks and the curved lamellar structures, were identified. Additionally, the orientation parameters indicating the alignments of the polymer chains were calculated and correlated with the morphologies.     

Fluid density profile transitions and symmetry breaking in a closed nanoslit

The density profiles in a fluid interacting with the two identical solid walls of a closed long slit were calculated for wide ranges of the number of fluid molecules in the slit and temperature by employing density functional theory in the local density approximation. Two potentials, the van der Waals and the Lennard-Jones, were considered for the fluid-fluid and the fluid-walls interactions. It was shown that the density profile corresponding to the stable state of the fluid considerably changes its shape with increasing average density (rhoav) of the fluid inside the slit, the details of changes being dependent on the selected potential. For the van der Waals potential, a single temperature-dependent critical value rhosb of rhoav was identified, such that for rhoav < rhosb the stable state of the system is described by a symmetric density profile, whereas for rhoav >/= rhosb it is described by an asymmetric one. This transition constitutes a spontaneous symmetry breaking of the fluid density distribution in a closed slit with identical walls. For rhoav >/= rhosb, a metastable state, described by a symmetric density profile, was present in addition to the stable asymmetric one. The shape of the symmetric profile changed suddenly at a value rhoc-h > rhosb of the average density, the density rhoc-h being almost independent of temperature. Because of the shapes of the profiles before and after the transformation, this transition was named cup-hill transformation. At the transition point, the density of the fluid near the walls decreased suddenly from a liquid-like value becoming comparable with the density of a gaseous phase, and the density in the middle of the slit increased suddenly from a gaseous-like value becoming on the order of the density of a liquid phase. For the Lennard-Jones potential, there are two temperature-dependent critical densities, rhosb1 and rhosb2, such that the stable density profile is asymmetric (symmetry breaking occurs) for rhosb1 相似文献   

Aptamer-modified DNA tetrahedra-gated metal–organic framework nanoparticle carriers for enhanced chemotherapy or photodynamic therapy

UiO-66 metal–organic framework nanoparticles (NMOFs) gated by aptamer-functionalized DNA tetrahedra provide superior biomarker-responsive hybrid nano-carriers for biomedical applications. Hybrid nano-carriers consisting of ATP-aptamer or VEGF-aptamer functionalized tetrahedra-gated NMOFs are loaded with the chemotherapeutic drug, doxorubicin (DOX). In the presence of ATP or VEGF, both abundant in cancer cells, the tetrahedra-gated NMOFs are unlocked to release the drug. Enhanced and selective permeation of the DOX-loaded ATP/VEGF-responsive tetrahedra-gated NMOFs into MDA-MB-231 breast cancer cells as compared to the reference ATP/VEGF-responsive duplex-gated NMOFs or non-malignant MCF-10A epithelial breast cells is observed. This results in enhanced and selective cytotoxicity of the tetrahedra-gated DOX-loaded NMOFs toward the malignant cells. Additional nano-carriers, consisting of photosensitizer Zn(ii) protoporphyrin IX (Zn(ii)-PPIX)-loaded VEGF-responsive tetrahedra-gated NMOFs, are introduced. The VEGF-triggered unlocking of the NMOFs yields separated G-quadruplex-VEGF aptamer complexes conjugated to the tetrahedra, resulting in the release of loaded Zn(ii)-PPIX. Association of the released Zn(ii)-PPIX to the G-quadruplex structures generates highly fluorescent supramolecular Zn(ii)-PPIX/G-quadruplex VEGF aptamer-tetrahedra structures. The efficient and selective generation of the highly fluorescent Zn(ii)-PPIX/G-quadruplex VEGF aptamer-tetrahedra nanostructures in malignant cells allows the light-induced photosensitized generation of reactive oxygen species (ROS), leading to high-efficacy PDT treatment of the malignant cells.

UiO-66 metal–organic framework nanoparticles (NMOFs) gated by aptamer-functionalized DNA tetrahedra provide superior biomarker-responsive hybrid nano-carriers for biomedical applications.