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.     

Laser beam transmission and focusing inside media

A mathematical model for analyzing laser beam transmission and focusing inside media is developed. The reflection and refraction on the interface between two different media and the absorption inside media are considered. Based on the mathematical model a computer program, which allows us to analyze the focusing and transmission processes of laser beam as well as to obtain the beam parameters and intensity profile inside media, is created.     

Photonuclear reactions on 112,118,124Sn,natTe, and natHf targets

The yields of products of photonuclear reactions on tin targets enriched in the isotopes ^112,118,124Sn and on Te and HfO₂ targets of natural isotopic composition were measured. The targets were irradiated at the linear electron accelerator of the A.I. Alikhanian National Science Laboratory (Yerevan Physics Institute) at the electron energy of E _e = 40 MeV. The dependence of the product yields on the nucleonic composition of the targets was discussed. The isomeric ratios were obtained for the ^119m,g Te, ^121m,g Te, ^117m,g In, and ^123m,g Sn products. The experimental data in question were compared with their theoretical counterparts calculated on the basis of the TALYS 1.4 code. The dependence of the isomeric ratios on the photon energy and on the mass number of the product is considered.     

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The different empirical models of light absorption in silicon by free charge carriers in near-infrared and infrared regions are analyzed. An improved empirical model for free carrier absorption in silicon is developed. Results are obtained over the wavelength range from 0.9 μm to 6 μm for n-type, and from 0.9 μm to 8 μm for p-type silicon. The new model is assessed ed by R ² parameter and the sufficient fitting of the experimental data is presented.     

Synthesis of Some Heterocyclic Compounds from Enamines of 3-Acetylfuran-2(5 H)-ones

The interaction of different 3-acetylfuran-2(5H)-ones (1, 4) with dimethylformamide dimethyl acetal (DMF/DMA) has been investigated, and the condensed furopyridine system 3 was obtained. By means of interaction of compounds 4 and DMF/DMA via the 3-acetylfuran-2(5H)-one enamines, the heterocyclic substituted furanones are obtained. The condensation of 3-acetyl-4,5,5-trimethylfuran-2(5H)-one (1a) with veratraldehyde was realized. Through the interaction of 1a with malononitrile and further intramolecular condensation of the product, 6-amino-dihydroisobenzofuran-5-carbonitrile was also synthesized.     

Synthesis of pyridone-substituted furan-2(5H)-ones and their intramolecular cyclization to afford furo[3,4-f]isoquinolines

Chemistry of Heterocyclic Compounds - Synthetic approach toward pyridone-substituted furan-2(5H)-ones has been described. Intramolecular cyclization of these compounds leads to novel 7-substituted...