Hydrogen bond networks determine emergent mechanical and thermodynamic properties across a protein family

Background

Gram-negative bacteria use periplasmic-binding proteins (bPBP) to transport nutrients through the periplasm. Despite immense diversity within the recognized substrates, all members of the family share a common fold that includes two domains that are separated by a conserved hinge. The hinge allows the protein to cycle between open (apo) and closed (ligated) conformations. Conformational changes within the proteins depend on a complex interplay of mechanical and thermodynamic response, which is manifested as an increase in thermal stability and decrease of flexibility upon ligand binding.

Results

We use a distance constraint model (DCM) to quantify the give and take between thermodynamic stability and mechanical flexibility across the bPBP family. Quantitative stability/flexibility relationships (QSFR) are readily evaluated because the DCM links mechanical and thermodynamic properties. We have previously demonstrated that QSFR is moderately conserved across a mesophilic/thermophilic RNase H pair, whereas the observed variance indicated that different enthalpy-entropy mechanisms allow similar mechanical response at their respective melting temperatures. Our predictions of heat capacity and free energy show marked diversity across the bPBP family. While backbone flexibility metrics are mostly conserved, cooperativity correlation (long-range couplings) also demonstrate considerable amount of variation. Upon ligand removal, heat capacity, melting point, and mechanical rigidity are, as expected, lowered. Nevertheless, significant differences are found in molecular cooperativity correlations that can be explained by the detailed nature of the hydrogen bond network.

Conclusion

Non-trivial mechanical and thermodynamic variation across the family is explained by differences within the underlying H-bond networks. The mechanism is simple; variation within the H-bond networks result in altered mechanical linkage properties that directly affect intrinsic flexibility. Moreover, varying numbers of H-bonds and their strengths control the likelihood for energetic fluctuations as H-bonds break and reform, thus directly affecting thermodynamic properties. Consequently, these results demonstrate how unexpected large differences, especially within cooperativity correlation, emerge from subtle differences within the underlying H-bond network. This inference is consistent with well-known results that show allosteric response within a family generally varies significantly. Identifying the hydrogen bond network as a critical determining factor for these large variances may lead to new methods that can predict such effects.     

Spin-glass behaviour in the coordination polymer [Co(C3H3N2)2]n

The magnetic behaviour of the coordination polymer [Co(C(3)H(3)N(2))(2)](n) has been investigated by magnetization and specific heat measurements. Low-field magnetic susceptibility shows the presence of two maxima at approximately 8 and 4 K (T(f)), which reflect short-range low-dimensional antiferromagnetic behaviour and the existence of a spin-glass-like state, respectively. The latter state was observed by magnetic irreversibility in both the zero-field cooled and field-cooled data, and was also confirmed by specific heat measurements. The magnetic specific heat (C(mag)) shows a lack of any long-range ordered peaks. Instead, a broad maximum near T(f) was observed in the C(mag)(T)/T-curve. Below T(f), the C(mag)(T) data follow the relation: C(mag)(T)/T = gamma + AT. We suggest that the competition of the antiferromagnetic (AF) intra-chain and the ferromagnetic (F) inter-chain interactions in a low-dimensional arrangement of magnetic Co(2+) ions can produce the spin-glass behaviour in the sample. The susceptibility data was analyzed in terms of a spin S = 3/2 Heisenberg linear-chain model with a small exchange energy and is consistent with the presence of both F and AF interactions. The splitting of the crystal field energy levels of the Co(2+) ions causes a Schottky-type specific heat anomaly of around 60 K.     

Library of biphenyl privileged substructures using a safety-catch linker approach

A biphenyl privileged structure library containing three attachment points were synthesized using a catechol-based safety-catch linker strategy. The method requires the attachment of a bromo-acid to the linker, followed by a Pd-catalyzed Suzuki cross-coupling reaction. Further derivatization, activation of the linker with strong acid and aminolysis afforded the respective products in high purity and good overall yield. To show the versatility of the synthesis, a 199-member library was generated. The library samples both conformational and chemical diversity about a well-known privileged substructure.     

The promotion effect of titania nanoparticles on the direct electrochemistry of lactate dehydrogenase sol-gel modified gold electrode

The promotion effect of titania nanoparticles (nano-TiO(2)) on the direct electron transfer between lactate dehydrogenase (LDH) and the silica sol-gel modified gold electrode was investigated by adding nano-TiO(2) (50 nm) in the modification process. This nano-TiO(2)-LDH electrode showed a pair of quasi-reversible cyclic voltammetry peaks with the formal potential of 70 mV (vs. SCE). Compared to the previous result of LDH modified electrode with only an irreversible cathodic peak, an anodic peak appeared and the cathodic peak potential shifted to the positive direction on this nano-TiO(2)-LDH electrode, which demonstrated that the direct electrochemistry of LDH was enhanced by nano-TiO(2). We supposed that the direct electrochemistry of LDH may be due to the redox reaction of some electroactive amino acids in the LDH molecule. The surface morphologies of electrodes characterized by SEM indicated that LDH was successfully immobilized on the sol-gel matrix and also had some interactions with nano-TiO(2). This electrode can be used as a biosensor for the determination of lactic acid. The calibration range of lactic acid was from 1.0 to 20 micromolL(-1) and the detection limit was 0.4 micromolL(-1). Meanwhile, the small K(m)(app) value (2.2 micromolL(-1)) suggested that LDH possessed high enzymatic activity and good affinity to lactic acid owing to the promotion effect of nano-TiO(2).     

Recent innovations in protein separation on microchips by electrophoretic methods

Microchips for analytical purposes have attracted great attention over the last 20 years. In the present review, we focus on the most recent development of microchips for electrophoretic separation of proteins. This review starts with a short recalling about the microchips covering the basic microchip layout for CE and the commercial chips and microchip platforms. A short paragraph is dedicated to the surface treatment of microchips, which is of paramount importance in protein analysis. One section is dedicated to on-line sample pretreatment in microchips and summarizes different strategies to pre-concentrate or to purify proteins from complex matrixes. Most of the common modes used for CE of proteins have already been adapted to the chip format, while multidimensional approaches are still in progress. The different routes to achieve detection in microchip are also presented with a special attention to derivatization or labeling of proteins. Finally, several recent applications are mentioned. They highlight the great potential of electrophoretic separations of proteins in numerous fields such as biological, pharmaceutical or agricultural and food analysis. A bibliography with 151 references is provided covering papers published from 2000 to the early 2007.     

对苯二甲酸二苯酯类液晶化合物光谱和二阶非线性光学性质的理论研究

在密度泛函理论B3LYP/6-31G*水平上计算对苯二甲酸二苯酯类液晶化合物分子的几何结构、振动光谱、电子光谱和非线性光学性质, 分析讨论端接基对其光谱与非线性光学性质的影响. 结果表明, 端接基的引入对该类分子的几何结构影响不大. 烷氧基的链长对分子振动光谱的影响很小, 端基引入CN时, C＝O的伸缩振动频率蓝移9 cm^－1. TD-DFT计算表明, 最大吸收光谱源于分子中HOMO→LUMO的p→p*跃迁, 对应的最大吸收波长值在313～375 nm之间, 属于紫外区. 端接强供电子基团可以提高分子的二阶非线性光学性质.     

Fabrication and characteristics of organic semiconductor nanoparticles of copper phthalocyanine oligomers

Nanoparticles of copper phthalocyanine oligomers (O-CuPc) with peripheral carboxylic acid groups have successfully been prepared by a simple method of liquid phase direct precipitation in the presence of different surfactants. X-ray diffraction patterns, transmission electron microscopy, and UV-visible spectra are employed to characterize the novel organic nanoparticles. The sizes and size distribution of the resulting O-CuPc nanoparticles show a noticeable dependence on surfactants. Nonionic surfactant is helpful in forming uniform nanoparticles. Also we observe a remarkable nanosize effect of the O-CuPc particles.