Low-radii transitions in co-assembled cationic-anionic cylindrical aggregates

We investigate the formation of charged patterns on the surface of cylindrical micelles from co-assembled cationic and anionic amphiphiles. The competition between the net incompatibility chi (which arises from the different chemical nature of oppositely charged molecules) and electrostatic interactions (which prevent macroscopic segregation) results in the formation of surface domains. We employ Monte Carlo simulations to study the domains at thermal equilibrium. Our results extend previous work by studying the effect of the Bjerrum length l(B) at different values of the cylinder's radius R and chi and analyze how it affects the transition between helical, ring, and isotropic patterns. A critical surface in the space (l(B), R, chi) separating these three phases is found, and we show how it corresponds to a first-order phase transition. This confirms that the Bjerrum length l(B) is a significant parameter in the control of the helical-ring transition; the ring pattern is strongly associated with short-range forces, whereas the helical pattern develops from dominant long-range electrostatic interactions.     

Thermodynamic and structural basis of phosphorylation-induced disorder-to-order transition in the regulatory light chain of smooth muscle myosin

We have performed molecular dynamics simulations of the phosphorylation domain (PD) of the regulatory light chain (RLC) of smooth muscle myosin, to gain insight into the thermodynamic principles governing the phosphorylation-induced disorder-to-order transition. Simulations were performed in explicit water under near-physiological conditions, starting with an ideal alpha-helix. In the absence of phosphorylation, the helical periodicity of the peptide was disrupted at residues T9-K11, while phosphorylation significantly favored the helical periodicity, in agreement with experimental data. Using the MM/PBSA approach, we calculated a relative free energy of -7.1 kcal/mol for the disorder-to-order transition. A large enthalpic decrease was compensated by a large loss of conformational entropy, despite the small helical increase (no more than three residues) upon phosphorylation. Phosphorylation decreased the conformational dynamics of K and R side chains, especially R16, which forms a salt bridge with pS19. Mutation of R16 to A or E prevented this phosphorylation-dependent ordering. We propose that phosphorylation balances the enthalpy-entropy compensation of the disorder-to-order transition of RLC via short and long-range electrostatic interactions with positively charged residues of the phosphorylation domain. We suggest that this balance is necessary to induce a disorder-to-order conformational change through a subtle energy switching.     

Amyloid Polymorphism in the Protein Folding and Aggregation Energy Landscape

Protein folding involves a large number of steps and conformations in which the folding protein samples different thermodynamic states characterized by local minima. Kinetically trapped on‐ or off‐pathway intermediates are metastable folding intermediates towards the lowest absolute energy minima, which have been postulated to be the natively folded state where intramolecular interactions dominate, and the amyloid state where intermolecular interactions dominate. However, this view largely neglects the rich polymorphism found within amyloid species. We review the protein folding energy landscape in view of recent findings identifying specific transition routes among different amyloid polymorphs. Observed transitions such as twisted ribbon→crystal or helical ribbon→nanotube, and forbidden transitions such helical ribbon?crystal, are discussed and positioned within the protein folding and aggregation energy landscape. Finally, amyloid crystals are identified as the ground state of the protein folding and aggregation energy landscape.     

Reversible Ligand-Gated Ion Channel via Interconversion between Hollow Single Helix and Intertwined Double Helix

Ligand responsiveness is one of the typical mechanisms in biological organization to trigger sophisticated channel switching. Here, we report a new type of helical trimer which can undergo transition between a hollow single helix and an intertwined double helix with no cavity by complexation and decomplexation of Cu ions. In addition, the one dimensional (1D) hollow helical tubes spontaneously generated from single helices via π-π interactions embedded into the lipid bilayers and displayed satisfactory channel stability and efficiency. With the addition of Cu^I ions and further extraction with ammonia, the disassembly and reassembly of 1D hollow helical tubes gave rise to the reversible switching of channel activity in situ inside the bilayers. The synthetic helical system provides the first model of reversible ligand-gated ion channel by means of dynamic transition between single and double helices, which will be available for developing intelligent artificial nanochannels for potential biological and medicinal applications.     

Reversible Ligand‐Gated Ion Channel via Interconversion between Hollow Single Helix and Intertwined Double Helix

Ligand responsiveness is one of the typical mechanisms in biological organization to trigger sophisticated channel switching. Here, we report a new type of helical trimer which can undergo transition between a hollow single helix and an intertwined double helix with no cavity by complexation and decomplexation of Cu ions. In addition, the one dimensional (1D) hollow helical tubes spontaneously generated from single helices via π‐π interactions embedded into the lipid bilayers and displayed satisfactory channel stability and efficiency. With the addition of Cu^I ions and further extraction with ammonia, the disassembly and reassembly of 1D hollow helical tubes gave rise to the reversible switching of channel activity in situ inside the bilayers. The synthetic helical system provides the first model of reversible ligand‐gated ion channel by means of dynamic transition between single and double helices, which will be available for developing intelligent artificial nanochannels for potential biological and medicinal applications.     

How does the coupling of secondary and tertiary interactions control the folding of helical macromolecules?

The authors study how the simultaneous presence of short-range secondary and long-range tertiary interactions controls the folding and collapse behavior of a helical macromolecule. The secondary interactions stabilize the helical conformation of the chain, while the tertiary interactions govern its overall three-dimensional shape. The authors have carried out Monte Carlo simulations to study the effect of chain length on the folding and collapse behavior of the chain. They have calculated state diagrams for four chain lengths and found that the physics is very rich with a plethora of stable conformational states. In addition to the helix-coil and coil-globule transitions, their model describes the coupling between them which takes place at low temperatures. Under these conditions, their model predicts a cascade of continuous, conformational transitions between states with an increase in the strength of the tertiary interactions. During each transition the chain shrinks, i.e., collapses, in a rapid and specific manner. In addition, the number of the transitions increases with increasing chain length. They have also found that the low-temperature regions of the state diagram between the transition lines cannot be associated with specific structures of the chain, but rather, with ensembles of various configurations of the chain with similar characteristics. Based on these results the authors propose a mechanism for the folding and collapse of helical macromolecules which is further supported by the analysis of configurational, configurational, and thermodynamic properties of the chain.     

Theoretical determination of helix-coil parameter sigma from a model of partly helical polypeptide chain.

The Zimm and Bragg parameter sigma is calculated numerically for poly(L-alanine), polyglycine, and the copolymers of L-alanine and glycine using the molecular theory of s and sigma as developed by Go, Go, and Scheraga in a modified formulation. In this formulation, sigma is obtained from the partition function of the whole chain in the helix-coil transition region and represents therefore the contributions from the ends of helical and coil sequences and from the interactions between atoms in a coil sequence with those in the neighboring helical sequence. When the parameter sigma is calculated numerically from a hard-sphere potential, it appears that steric intractions between atoms in the coil sequence with atoms in the neighboring helical sequence, which have been neglected in previous calculations, contribute significantly to the value of sigma. Owing to these interactions the entropy of the coil sequence as well as sigma decrease, but the decrease of sigma is larger in poly(L-alanine) than in polyglycine, because of the higher flexibility of the monomer in polyglycine. The numerical value of sigma for polyglycine compared with that of poly(L-alanine) might be overestimated however by the model presented here due to approximations inherent in the hard-sphere treatment and because only regular helical sequences are considered.     

Two scale generalized model of polypeptide chains

The generalized model of polypeptide chains (GMPC) is expanded to simultaneously consider two types of interactions occurring over different scales. This new two scale GMPC is applied in several specific cases to examine: The combined influence of stacking or antistacking and hydrogen bonding, or spatial restrictions on the length of helical segments, on the cooperativity and temperature interval of the helix-coil transition of duplex DNA. For the cases of stacking or antistacking in combination with hydrogen bonding the model reduces to the basic uniscale model with a redefined scaling parameter Delta. Antistacking increases the cooperativity, while stacking decreases it. In each case, explanations are given in terms of different lengths of helical segments. Restrictions on the length of helical regions result in the appearance of antiferromagnetic-type correlations where there is no apparent link between cooperativity and transition interval.     

Structure of single and double stranded dna solutions as studied by ultracentrifugation

The osmotic pressure of dense solutions of DNA fragments in aqueous 0.2-2 M salt (NaCl, etc.) solutions were easily obtained from equilibrium ultracentrifugation data. Short, helical double stranded DNA fragment solutions showed a well defined ordering transition. The osmotic pressure of these helical solutions could be explained by the scaled particle theory of rigid sphero-cylinders. On the other hand, dense solutions of (single stranded) etheno-DNA derivatives (of about 100 nucleotides) showed no ordering phase transition. The osmotic pressure as a function of the ε-DNA concentration verifies a scaling prediction for random coils in the semi-dilute regime. Good fits to the reduced osmotic pressure are obtained by using the Kleintjens and Koningsveld modified mean field lattice gas equations of state. As inferred from the Zimm clustering function, essentially all intermolecular interactions at high ionic strength are purely repulsive.     

Crystallization of helical oligomers with chirality selection. I. A molecular dynamics simulation for bare helix

Helical polymers often exhibit pronounced chirality recognition during crystallization. By molecular dynamics simulation, we have already shown that the helical polymers crystallize with or without marked chirality selection depending on structural details of the polymer molecules. We have there classified the helical polymers into two categories: the bare helices made of only backbone atoms which show rather tolerant chirality selection, and the general helices with large side groups showing strict chirality recognition. Polymer crystallization is in general largely hampered and retarded by slow dynamics of the entangled chains, and therefore short helical oligomers are very suitable models for studying the chiral crystallization. We here report on molecular simulations of crystallization in the bare helical oligomer molecules by the use of Monte Carlo and molecular dynamics simulations. First we confirm the low temperature chiral crystal phase and the reversible order-disorder transition. We also observe frequent inversions of the helical sense, and the helix reversal defects propagating along the chains. Then we investigate crystallization from the melt into the chiral crystal phase. We find that the crystallization rate depends very sensitively on the degree of undercooling. The crystallization is found to be the first order transition that conforms well to the traditional picture of crystal growth in small molecules. Even when the crystallization directly into the chiral crystal phase is conducted, marked chirality selections are not observed at the early stage of crystallization; the chains adhere to the crystal surfaces selecting their helical senses rather at random resulting in racemic crystallites. The isothermal crystallization for a sufficiently long time, however, yields lamellar crystals composed of well-developed chiral domains, the growth of which seems to be accomplished through the transition back into the ordered chiral crystal phase.     

Helix formation in the polymer brush

This work considers the physics of a brush formed by polymers capable of undergoing a helix-coil transition. A self-consistent field approximation for strongly stretched polymer chains is used in combination with a lattice model of the interaction energy in helix-coil mixtures. Crowding-induced chain stretching stabilizes helix formation at moderate tethering densities while high tethering density causes sufficiently strong stretching to unravel segments of the helix, resulting in distinct layers of monomer density and helical content. Compared to a random-coil brush at low-to-moderate tethering density, a helicogenic brush is less resistant to compression in the direction perpendicular to stretching due to easy alignment of helices and fewer unfavorable interactions between helical segments. At higher tethering density, the abovementioned stretch-induced decrease in helical content resists further compression. The proposed model is useful for understanding an emerging class of biomaterials that utilize helix-forming polymer brushes to induce shape changes or to stabilize biofunctional helical peptide sequences.     

A minimal proteinlike lattice model: an alpha-helix motif

A simple protein model of a four-helix bundle motif on a face-centered cubic lattice has been studied. Total energy of a conformation includes attractive interactions between hydrophobic residues, repulsive interactions between hydrophobic and polar residues, and a potential that favors helical turns. Using replica exchange Monte Carlo simulations we have estimated a set of parameters for which the native structure is a global minimum of conformational energy. Then we have shown that all the above types of interactions are necessary to guarantee the cooperativity of folding transition and to satisfy the thermodynamic hypothesis.     

Origin of enantioselectivity in the propargylation of aromatic aldehydes catalyzed by helical N-oxides

The enantioselective propargylation of aromatic aldehydes with allenyltrichlorosilanes catalyzed by bipyridine N-oxides was explored using density functional theory. Low-lying transition states for a highly enantioselective helical bipyridine N-oxide catalyst [Org. Lett. 2011, 13, 1654] were characterized at the B97-D/TZV(2d,2p) level of theory. Predicted free energy barrier height differences are in agreement with experimental ee's for the propargylation of benzaldehyde and substituted analogues. The origin of enantioselectivity was pinpointed through distortion-interaction analyses. The stereoselectivity arises in part from through-space electrostatic interactions of the carbonyl carbon with the Cl ligands bound to Si, rather than noncovalent aryl-aryl interactions between the aromatic aldehyde and the helix as previously proposed. Moreover, aryl-aryl interactions between the aldehyde and helix are predicted to favor transition states leading to the R enantiomer, and ultimately reduce the enantioselectivity of this reaction. (S)-2,2'-bipyridine N-oxide was studied as a model catalyst in order to quantify the inherent enantioselectivity arising from different chiral arrangements of ligands around the hexacoordinate silicon in the stereocontrolling transition state for these reactions. The predicted selectivities arising from different chiral octahedral silicon complexes provide guidelines for the development of transition state models for N-oxide-based alkylation catalysts.     

无机-有机复合聚合物:材料研究的一个新领域

无机-有机复合聚合物特别是类分子筛聚合物、类多层钙钛矿和仿生物材料的合成及其应用研究成为近几年来一个热门的研究领域。我们瞄准了这一前沿领域并合成和表征了以下四个系列具有纳米孔洞的分子笼和一维、二维或三维的新型无机聚合物:(1)带有纳米尺寸空腔和孔状结构的新型过渡金属和稀土金属聚合物;(2)含有螺旋链的一维链状聚合物;(3)具有石墨形态层状结构和优异导电性能的聚合物;(4)以强金属-金属相互作用为核心、有机分子为稳定外壳的纳米线聚合物。本文总结这四个系列化合物的合成结构和特性。     

Amplification of Chirality in Helical Supramolecular Columns

Strong amplification of chirality occurs in dynamic, but highly ordered, helical columns in n-butanol, for which one chiral seed molecule suffices to render a column of 400 molecules to become homochiral. The chiral columns are formed in a thermally dependent stepwise process. The transition from achiral stacks to helical columns is highly cooperative owing to well-defined intermolecular interactions. `Sergeant and Soldiers' measurements allow for the calculation of the association constant and cooperativity length of the homochiral segments. The `Sergeant and Soldiers' data on the number of molecules within a column show a strikingly good match with data obtained from a theoretical model describing the self-assembly of the discotic molecules as a function of temperature and concentration.     

Shear-induced conformational ordering, relaxation, and crystallization of isotactic polypropylene

The shear-induced coil-helix transition of isotactic polypropylene (iPP) has been studied with time-resolved Fourier transform infrared spectroscopy at various temperatures. The effects of temperature, shear rate, and strain on the coil-helix transition were studied systematically. The induced conformational order increases with the shear rate and strain. A threshold of shear strain is required to induce conformational ordering. High temperature reduces the effect of shear on the conformational order, though a simple correlation was not found. Following the shear-induced conformational ordering, relaxation of helices occurs, which follows the first-order exponential decay at temperatures well above the normal melting point of iPP. The relaxation time versus temperature is fitted with an Arrhenius law, which generates an activation energy of 135 kJ/mol for the helix-coil transition of iPP. At temperatures around the normal melting point, two exponential decays are needed to fit well on the relaxation kinetic of helices. This suggests that two different states of helices are induced by shear: (i) isolated single helices far away from each other without interactions, which have a fast relaxation kinetic; (ii) aggregations of helices or helical bundles with strong interactions among each other, which have a much slower relaxation process. The helical bundles are assumed to be the precursors of nuclei for crystallization. The different helix concentrations and distributions are the origin of the three different processes of crystallization after shear. The correlation between the shear-induced conformational order and crystallization is discussed.     

Folding of coordination polymers into double-stranded helical organization

Self-assembling coordination polymers based on Pd II and Cu II metal ions were prepared from complexation of a bent-shaped bispyridine ligand and a corresponding transition metal. These coordination polymers were observed to self-assemble into supramolecular structures that differ significantly depending on the coordination geometry of the metal center. The polymer based on Pd II self-assembles into a layer structure formed by bridging bispyridine ligands connected in a trans-position of the square-planar coordination geometry of metal center. In contrast, the polymer based on Cu II adopts a double-helical conformation with regular grooves, driven by interstranded, copper-chloride dimeric interaction. The double-stranded helical organization is further confirmed by structure optimization from density functional theory with aromatic framework, showing that the optimized double-helical structure is energetically favorable and consistent with the experimental results. These results demonstrate that weak metal-ligand bridging interactions can provide a useful strategy to construct stable double-stranded helical nanotubes.     

In Vitro Reconstitution of a Cellular Phase‐Transition Process that Involves the mRNA Decapping Machinery

In eukaryotic cells, components of the 5′ to 3′ mRNA degradation machinery can undergo a rapid phase transition. The resulting cytoplasmic foci are referred to as processing bodies (P‐bodies). The molecular details of the self‐aggregation process are, however, largely undetermined. Herein, we use a bottom‐up approach that combines NMR spectroscopy, isothermal titration calorimetry, X‐ray crystallography, and fluorescence microscopy to probe if mRNA degradation factors can undergo phase transitions in vitro. We show that the Schizosaccharomyces pombe Dcp2 mRNA decapping enzyme, its prime activator Dcp1, and the scaffolding proteins Edc3 and Pdc1 are sufficient to reconstitute a phase‐separation process. Intermolecular interactions between the Edc3 LSm domain and at least 10 helical leucine‐rich motifs in Dcp2 and Pdc1 build the core of the interaction network. We show that blocking of these interactions interferes with the clustering behavior, both in vitro and in vivo.     

Phase transition of nanotube-confined water driven by electric field

The effects of electric field on the phase behaviors of water encapsulated in a thick single-walled carbon nanotube (SWCNT) (diameter = 1.2 nm) have been studied by performing extensive molecular dynamics simulations at atmospheric pressure. We found that liquid water can freeze continuously into either pentagonal or helical solidlike ice nanotube in SWCNT, depending on the strengths of the external electric field applied along the tube axis. Remarkably, the helical one is new ice phase which was not observed previously in the same size of SWCNT in the absence of electric field. Furthermore, a discontinuous solid-solid phase transition is observed between pentagonal and helical ice nanotubes as the strengths of the external electric field changes. The mechanism of electric-field-induced phase transition is discussed. The dependence of ice structures on the chiralities of SWCNTs is also investigated. Finally, we present a phase diagram of confined water in the electric field-temperature plane.     

Confocal fluorescence imaging of photosensitized DNA denaturation in cell nuclei

The double-stranded helical structure of DNA is maintained in part by hydrogen bonds between strands and by stacking interactions between adjacent purine and pyrimidine bases in one strand. The transition (denaturation) from a double-stranded (ds) to a single-stranded (ss) form can be induced in isolated DNA or fixed cells by exposure to elevated temperatures, alkali or acids, aprotic or nonpolar solvents or some drugs. We report here that DNA denaturation can occur in situ in cell nuclei as a result of interaction between light and an intercalated dye, acridine orange or ethidium bromide. This DNA photodenaturation was probed using metachromatic properties of acridine orange and imaged by fluorescence confocal microscopy. Furthermore, an empirical kinetic model was developed to separate changes of acridine orange luminescence intensities caused by photobleaching from those that were a result of DNA denaturation. We investigated the influence of oxygen on these phenomena and propose a mechanism by which photodenaturation may occur.