Tryptophan side chain electrostatic interactions determine edge-to-face vs parallel-displaced tryptophan side chain geometries in the designed beta-hairpin "trpzip2"

The interaction geometries of the four tryptophan (Trp) side chains in the 12-residue designed beta-hairpin trpzip2 are investigated using all-atom explicit-solvent molecular dynamics simulations. The experimentally observed edge-to-face (EtF) pairwise interaction geometries are stable on a time scale of 10 ns. However, removing the electrostatic multipoles of the Trp side chains while retaining the dipoles of the side chains' NH moieties induces a conformational change to a geometry in which three of the four side chains interact in a parallel-displaced (PD) manner. Free energy simulations of the Etf to PD conformational change reveal that, with the side chain multipole moments intact (+MP), the EtF conformation is preferred by 5.79 kcal/mol. Conversely, with only the dipole moments of the side chain NH moieties intact (-MP), the PD conformation's free energy is more favorable by 1.71 kcal/mol. In contrast to energetic similarities for Trp side chain-water electrostatic and Trp side chain-Trp side chain and Trp side chain-water van der Waals, +MP Trp side chain-Trp side chain electrostatic interactions are more favorable by 4.21 kcal/mol in the EtF conformation, while in the -MP case the EtF and PD conformations' Trp side chain-Trp side chain electrostatic energies are nearly identical. The results highlight the importance of electrostatic multipole moments in determining aromatic-aromatic interaction geometries in aqueous biomolecular systems and argue for the inclusion of this physics in simplified models used for protein-ligand docking and protein structure prediction, possibly through a truncated Coulomb term between aromatic moieties.     

Structure and mobility of a series of poly(alkyl l-glutamate)s studied by VT 13C CPMAS NMR spectroscopy

VT CPMAS NMR measurements were carried out for a series of poly(alkyl l-glutamate)s (PALG) which have n-alkyl side chains with carbon numbers ranging from 2 to 12 in order to investigate the structure and mobility of the main and the side chains. From the temperature dependencies of the peak intensities for the PALGs, the relative mobilities of the main and side chains are discussed. For PG-2 and PG-4, the molecular motions of both the main and side chains are not very fast. From the amount ratio between the main and side chains, the main chain dominates the entire mobility of the polymer. As the side chain length increases, the side chain motion is drastically activated by a temperature change. In addition, the main chain motion is induced by the side chain motion. For PALGs with long alkyl side chains, the mobilities of the polymers are governed by the structure and mobility of the side chain.     

Importance of chirality and reduced flexibility of protein side chains: a study with square and tetrahedral lattice models

Side chains of amino acid residues are the determining factor that distinguishes proteins from other unstable chain polymers. In simple models they are often represented implicitly (e.g., by spin states) or simplified as one atom. Here we study side chain effects using two-dimensional square lattice and three-dimensional tetrahedral lattice models, with explicitly constructed side chains formed by two atoms of different chirality and flexibility. We distinguish effects due to chirality and effects due to side chain flexibilities, since residues in proteins are L residues, and their side chains adopt different rotameric states. For short chains, we enumerate exhaustively all possible conformations. For long chains, we sample effectively rare events such as compact conformations and obtain complete pictures of ensemble properties of conformations of these models at all compactness region. This is made possible by using sequential Monte Carlo techniques based on chain growth method. Our results show that both chirality and reduced side chain flexibility lower the folding entropy significantly for globally compact conformations, suggesting that they are important properties of residues to ensure fast folding and stable native structure. This corresponds well with our finding that natural amino acid residues have reduced effective flexibility, as evidenced by statistical analysis of rotamer libraries and side chain rotatable bonds. We further develop a method calculating the exact side chain entropy for a given backbone structure. We show that simple rotamer counting underestimates side chain entropy significantly for both extended and near maximally compact conformations. We find that side chain entropy does not always correlate well with main chain packing. With explicit side chains, extended backbones do not have the largest side chain entropy. Among compact backbones with maximum side chain entropy, helical structures emerge as the dominating configurations. Our results suggest that side chain entropy may be an important factor contributing to the formation of alpha helices for compact conformations.     

Liquid-crystalline polysiloxanes with fluoro-substituted side chains

Sixteen new side chain liquid polysiloxanes, either homopolymers derived from poly(hydrogenmethyl)siloxane or copolymers derived from poly(hydrogenmethyl-dimethylsiloxane), are reported with side chains carrying fluoro-substituents. The known effects of fluoro-substitution in low molar mass liquid crystals are strongly echoed in the polymeric analogues and interesting comparisons are made between homo- and co-polymers carrying the same fluorinated side chains.     

Intramolecular mobility of side chains of poly(methacrylic acid) in regularly grafted copolyimides in solution

A “dark” copolyimide with regularly grafted side chains of polymethacrylic acid and a luminescence-labeled copolyimide containing an anthracene label covalently attached to side chains with an average polycondensation degree of the polyimide backbone of ～16 and an average polymerization degree of side poly(methacrylic acid) chains of ～100 are synthesized. Relaxation times τ_IMM characterizing the mobility of parts of side chains in solvents of different thermodynamic qualities for the backbone and side chains are determined through the polarized luminescence method. It is shown that, in a “common” solvent for the backbone and side chains, the values of τ_IMM are close to those characterizing the mobility of linear polymethacrylate chains. In selective solvents, changes in τ_IMM are related to not only changes in intramolecular interactions but also changes in the heterogeneity of the dynamic characteristics of parts of grafted chains arranged at different distances from the grafting point.     

聚丙烯酸酯的玻璃化温度的定量结构性质相关研究

提出了高分子的侧基顺拉模型 ,认为侧基的空间效应主要来源于侧基的轴向横截面积 .与侧基的轴向横截面积密切相关的是侧基的碳链分支数 .直接采用侧基碳链分支数作为侧基的空间效应参数 ,对 13种聚丙烯酸酯和 9种聚甲基丙烯酸酯的玻璃化温度进行了定量结构 性质相关研究 ,得到了良好的三参数模型 ,对聚丙烯酸酯和聚甲基丙烯酸酯的玻璃化温度分别进行回归分析 ,相关系数R2 =0 989(s =3 8K)和R2 =0 993 (s =4 8K) .该模型对 2 2种聚丙烯酸酯和聚甲基丙烯酸酯的合并计算的结果是R2 =0 980 (s =8 3K) .建立的模型参数计算简便 ,模型的稳定性和适应性较好 ,所有模型的标准误差均小于或接近实验误差 .     

60例口服合心爽病例副作用观察

观察了６０例口服合心爽病例副作用症状，比国外报道严重，提出一些措施，可减轻副作用。     

Adsorption of comb copolymers on weakly attractive solid surfaces

In this work continuum and lattice Monte Carlo simulation methods are used to study the adsorption of linear and comb polymers on flat surfaces. Selected polymer segments, located at the tips of the side chains in comb polymers or equally spaced along the linear polymers, are attracted to each other and to the surface via square-well potentials. The rest of the polymer segments are modeled as tangent hard spheres in the continuum model and as self-avoiding random walks in the lattice model. Results are presented in terms of segment-density profiles, distribution functions, and radii of gyration of the adsorbed polymers. At infinite dilution the presence of short side chains promotes the adsorption of polymers favoring both a decrease in the depletion-layer thickness and a spreading of the polymer molecule on the surface. The presence of long side chains favors the adsorption of polymers on the surface, but does not permit the spreading of the polymers. At finite concentration linear polymers and comb polymers with long side chains readily adsorb on the solid surface, while comb polymers with short side chains are unlikely to adsorb. The simple models of comb copolymers with short side chains used here show properties similar to those of associating polymers and of globular proteins in aqueous solutions, and can be used as a first approximation to investigate the mechanism of adsorption of proteins onto hydrophobic surfaces.     

Thermolysis of Neopentylcobalamin Analogs Complexed to Haptocorrin: Side Chain Entropy and Activation of Organocobalamins for Carbon-Cobalt Bond Homolysis

The kinetics of the thermal Co-C bond homolysis of the complexes of a vitamin B(12) binding protein (haptocorrin) with a series of analogs of neopentylcobalamin modified in side chain structure have been studied. The analogs include the C13 epimer in which the e propionamide side chain adopts an "upwardly" axial conformation and a series of c side chain-modified analogs, including the c-monocarboxylate, the c-N-methylamide, the c-N,N-dimethylamide, and the c-N-isopropylamide. Activation parameters for the thermal homolysis of these complexes show that the previously observed stabilization of alkylcobalamins by haptocorrin is due to both enthalpic and entropic factors. With the exception of that for the analog having the bulkiest c side chain substituent, neopentylcobalamin-c-N-isopropylamide, the enthalpies of activation are independent of analog structure, but the entropies of activation increase with the steric bulk of the c side chain and with the number of "upwardly" projecting side chains, as previously observed for protein-free neopentylcobalamin and its analogs. The results are discussed in terms of the solvent cage effect on Co-C bond homolysis and the importance of corrin ring side chain thermal motions to the entropy of activation for this reaction.     

Two mechanisms of spontaneous curvature of strongly adsorbed (2D) double comblike copolymers

We propose a theory of spontaneous curvature of 2D comblike macromolecules with incompatible side chains of types A and B. It is expected that the side chains of both types are able to change their positions with respect to the backbone. We predict two mechanisms of curvature. In the case of strong incompatibility of the side chains, their complete segregation with respect to the backbone is responsible for the formation of the so-called "energetic" curvature that is a result of the difference in the length (or in the number) of the A and B chains. In the case of moderate incompatibility, partial mixing of the A and B side chains on the convex side of the molecule (a flip of shorter chains to the side of longer chains) can be entropically favorable. In this case, the stretching of the side chains decreases. The radius of the entropic curvature is determined by the length of the longer side chains.     

Simulation study of the equilibrium morphology in ionomers with different architectures

The influence of the side chain and the backbone segment length on the shape of the hydrophilic clusters in an ionomer with sulfonate‐terminated side chains is investigated by molecular dynamics computer simulations. Different ionomer architectures, ranging from Nafion‐like molecules to ionomer structures with extremely long side chains and backbone segments, are analyzed. It is shown that the size and the sulfonate population of hydrophilic clusters are differently affected by the variation of the backbone length in homologous membranes. Although the clusters swell when the backbone length is increased, they contain fewer head groups, and the average sulfonate–sulfonate separation in these swollen clusters becomes larger. An increase in the equivalent weight (EW) of homologous membranes thus hinders proton transport through hydrophilic channels. We also have shown that larger sulfonate clusters are formed in modified membranes with longer side chains. Compared to the case of membranes with shorter side chains but the same EW, those with longer side chains have a higher proton diffusivity. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2010     

A Monte Carlo simulation study of branched polymers

Monte Carlo simulations are presented for the static properties of highly branched polymer molecules. The molecules consist of a semiflexible backbone of hard-sphere monomers with semiflexible side chains, also composed of hard-sphere monomers, attached to either every backbone bead or every other backbone bead. The conformational properties and structure factor of this model are investigated as a function of the stiffness of the backbone and side chains. The average conformations of the side chains are similar to self-avoiding random walks. The simulations show that there is a stiffening of the backbone as degree of crowding is increased, for example, if the branch spacing is decreased or side chain length is increased. The persistence length of the backbone is relatively insensitive to the stiffness of the side chains over the range investigated. The simulations reproduce most of the qualitative features of the structure factor observed in experiment, although the magnitude of the stiffening of the backbone is smaller than in experiment.     

SYNTHESIS AND PHASE BEHAVIOUR OF CHIRAL COMBINED MAIN/SIDE CHAIN LIQUID CRYSTALLINE COPOLYMERS

The synthesis and phase behaviour of chiral combined main/side chain liquid crystallinecopolymers containing pendant group constituted by chiral side group and trans-azobenzenemoiety with nitro end group are described. The formation of liquid crystalline polymorphism ofcopolymers is influenced by various contents of achiral side group.     

Structural and energetic effects in the molecular recognition of protonated peptidomimetic bases by 18-crown-6

Absolute 18-crown-6 (18C6) affinities of nine protonated peptidomimetic bases are determined using guided ion beam tandem mass spectrometry techniques. The bases (B) included in this work are mimics for the n-terminal amino group and the side chains of the basic amino acids, i.e., the favorable sites for binding of 18C6 to peptides and proteins. Isopropylamine is chosen as a mimic for the n-terminal amino group, imidazole and 4-methylimidazole are chosen as mimics for the side chain of histidine (His), 1-methylguanidine is chosen as a mimic for the side chain of arginine (Arg), and several primary amines including methylamine, ethylamine, n-propylamine, n-butylamine, and 1,5-diamino pentane as mimics for the side chain of lysine (Lys). Theoretical electronic structure calculations are performed to determine stable geometries and energetics for neutral and protonated 18C6 and the peptidomimetic bases, as well as the proton bound complexes comprised of these species, (B)H(+)(18C6). The measured 18C6 binding affinities of the Lys side chain mimics are larger than the measured binding affinities of the mimics for Arg and His. These results suggest that the Lys side chains should be the preferred binding sites for 18C6 complexation to peptides and proteins. Present results also suggest that competition between Arg or His and Lys for 18C6 is not significant. The mimic for the n-terminal amino group exhibits a measured binding affinity for 18C6 that is similar to or greater than that of the Lys side chain mimics. However, theory suggests that binding to n-terminal amino group mimic is weaker than that to all of the Lys mimics. These results suggest that the n-terminal amino group may compete with the Lys side chains for 18C6 complexation.     

Conformations of molecular brushes based on polyimide and poly(methyl methacrylate) in selective solvents: Experiment and computer simulation

The effect of solvent quality with respect to main and side chains on the conformations of molecular brushes is investigated by the methods of molecular hydrodynamics and optics as well as by computer simulation. Copolymers with a polyimide backbone and poly(methyl methacrylate) side chains are studied in solvents featuring strongly different thermodynamic qualities (chloroform, ethyl acetate, and 3-heptanone). The studied samples have close total molecular masses and backbone lengths but differ in grafting densities and lengths of side chains: a brush with densely grafted and relatively short side chains versus a brush with loosely grafted but very long side chains. For both types of brushes, similar changes in hydrodynamic behavior with improvement in the solvent quality are found experimentally. Computer simulation shows that these changes have different origins. In the former case, macromolecules are elongated, and their volumes grow simultaneously, while in the latter case, the shape of the macromolecules remains close to spherical and the changes in hydrodynamic parameters are mainly due to an increase in the volume of macromolecules.     

Sensitivity enhancement of solid-state NMR spectra of half-integer spin quadrupolar nuclei: Double- or single-frequency sweeps? Insights from the hyperbolic secant experiment

Improved sensitivity enhancements of the central NMR transition of non-integer spin quadrupolar nuclei in MAS powder samples are realized when only a single satellite transition spinning side band is irradiated using a conventional double-frequency sweep experiment compared to irradiation of the entire spinning side band manifold. For example, for ⁸⁷Rb in RbClO₄, enhancement factors of 2.2 versus 1.9 are observed when only one satellite transition spinning side band is targeted versus the entire spinning side band manifold. Similarly, for ²⁷Al in Al(acac)₃, the corresponding enhancement was 3.4 compared to 2.6.     

Protein–ligand docking with multiple flexible side chains

In this work, we validate and analyze the results of previously published cross docking experiments and classify failed dockings based on the conformational changes observed in the receptors. We show that a majority of failed experiments (i.e. 25 out of 33, involving four different receptors: cAPK, CDK2, Ricin and HIVp) are due to conformational changes in side chains near the active site. For these cases, we identify the side chains to be made flexible during docking calculation by superimposing receptors and analyzing steric overlap between various ligands and receptor side chains. We demonstrate that allowing these side chains to assume rotameric conformations enables the successful cross docking of 19 complexes (ligand all atom RMSD < 2.0 A) using our docking software FLIPDock. The number of side receptor side chains interacting with a ligand can vary according to the ligand's size and shape. Hence, when starting from a complex with a particular ligand one might have to extend the region of potential interacting side chains beyond the ones interacting with the known ligand. We discuss distance-based methods for selecting additional side chains in the neighborhood of the known active site. We show that while using the molecular surface to grow the neighborhood is more efficient than Euclidian-distance selection, the number of side chains selected by these methods often remains too large and additional methods for reducing their count are needed. Despite these difficulties, using geometric constraints obtained from the network of bonded and non-bonded interactions to rank residues and allowing the top ranked side chains to be flexible during docking makes 22 out of 25 complexes successful.     

Cα-Cβ chromophore bond dissociation in protonated tyrosine-methionine, methionine-tyrosine, tryptophan-methionine, methionine-tryptophan and their sulfoxide analogs

C(α)-C(β) chromophore bond dissociation in some selected methionine-containing dipeptides induced by UV photons is investigated. In methionine containing dipeptides with tryptophan as the UV chromophore, the tryptophan side chain is ejected either as an ion or as a neutral fragment while in dipeptides with tyrosine, the tyrosine side chain is lost only as a neutral fragment. Mechanisms responsible for these fragmentations are proposed based on measured branching ratios and fragmentation times, and on the results of DFT/B3-LYP calculations. It appears that the C(α)-C(β) bond cleavage is a non-statistical dissociation for the peptides containing tyrosine, and occurs after internal conversion for those with tryptophan. The proposed mechanisms are governed by the ionization potential of the aromatic side chain compared to that of the rest of the molecule, and by the proton affinity of the aromatic side chain compared to that of the methionine side chain. In tyrosine-containing peptides, the presence of oxygen on sulfur of methionine presumably reduces the ionization potential of the peptide backbone, facilitating the loss of the side chain as a neutral fragment. In tryptophan-containing peptides, the presence of oxygen on methionyl-sulfur expedites the transfer of the proton from the side chain to the sulfoxide, which facilitates the loss of the neutral side chain.     

Surface properties of bottle-brush polyelectrolytes on mica: effects of side chain and charge densities

Surface properties of a series of cationic bottle-brush polyelectrolytes with 45-unit-long poly(ethylene oxide) side chains were investigated by phase modulated ellipsometry and surface force measurements. The evaluation of the adsorbed mass of polymer on mica by means of ellipsometry is complex due to the transparency of mica and its birefringence and low dielectric constant. We therefore employed a new method to overcome these difficulties. The charge and the poly(ethylene oxide) side chain density of the bottle-brush polymers were varied from zero charge density and one side chain per segment to one charge per segment and no side chains, thus spanning the realm from a neutral bottle-brush polymer, via a partly charged brush polyelectrolyte, to a linear fully charged polyelectrolyte. The adsorption properties depend crucially on the polymer architecture. A minimum charge density of the polymer is required to facilitate adsorption to the oppositely charged surface. The maximum adsorbed amount and the maximum side chain density at the surface are obtained for the polymer with 50% charged segments and the remaining 50% of the segments carrying poly(ethylene oxide) side chains. It is found that brushlike layers are formed when 25-50% of the segments carry poly(ethylene oxide) side chains. In this paper, we argue that the repulsion between the side chains results in an adsorbed layer that is non-homogeneous on the molecular level. As a result, not all side chains will contribute equally to the steric repulsion but some will be stretched along the surface rather than perpendicular to it. By comparison with linear polyelectrolytes, it will be shown that the presence of the side chains counteracts adsorption. This is due to the entropic penalty of confining the side chains to the surface region.     

Synthesis of penta-p-phenylenes with oligo(ethylene glycol) side chains

We report an efficient synthesis of a series of penta-p-phenylene derivatives with four side chains of various lengths, including deca(ethylene glycol) groups. The key feature of the synthesis is that the side chains are efficiently introduced in the last step, facilitating optimization of the side chains for different applications. Raman spectroscopy study indicates a similarly high rigidity for all these compounds, even those with long oligo(ethylene glycol) side chains. The deca(ethylene glycol)-substituted penta-p-phenylene derivatives are versatile building blocks for construction of nanometric, tripod-shaped adsorbates for biological applications.