Evolution of domain combinations in protein kinases and its implications for functional diversity

Protein kinases phosphorylating Ser/Thr/Tyr residues in several cellular proteins exert tight control over their biological functions. They constitute the largest protein family in most eukaryotic species. Protein kinases classified based on sequence similarity in their catalytic domains, cluster into subfamilies, which share gross functional properties. Many protein kinases are associated or tethered covalently to domains that serve as adapter or regulatory modules,naiding substrate recruitment, specificity, and also serve as scaffolds. Hence the modular organisation of the protein kinases serves as guidelines to their functional and molecular properties. Analysis of genomic repertoires of protein kinases in eukaryotes have revealed wide spectrum of domain organisation across various subfamilies of kinases. Occurrence of organism-specific novel domain combinations suggests functional diversity achieved by protein kinases in order to regulate variety of biological processes. In addition, domain architecture of protein kinases revealed existence of hybrid protein kinase subfamilies and their emerging roles in the signaling of eukaryotic organisms. In this review we discuss the repertoire of non-kinase domains tethered to multi-domain kinases in the metazoans. Similarities and differences in the domain architectures of protein kinases in these organisms indicate conserved and unique features that are critical to functional specialization. (C) 2009 Elsevier Ltd. All rights reserved.

Excitation energy transfer from a fluorophore to single-walled carbon nanotubes

We study the process of electronic excitation energy transfer from a fluorophore to the electronic energy levels of a single-walled carbon nanotube. The matrix element for the energy transfer involves the Coulombic interaction between the transition densities on the donor and the acceptor. In the Foumlrster approach, this is approximated as the interaction between the corresponding transition dipoles. For energy transfer from a dye to a nanotube, one can use the dipole approximation for the dye, but not for the nanotube. We have therefore calculated the rate using an approach that avoids the dipole approximation for the nanotube. We find that for the metallic nanotubes, the rate has an exponential dependence if the energy that is to be transferred, h is less than a threshold and a d(-5) dependence otherwise. The threshold is the minimum energy required for a transition other than the k(i,perpendicular to)=0 and l=0 transition. Our numerical evaluation of the rate of energy transfer from the dye pyrene to a (5,5) carbon nanotube, which is metallic leads to a distance of similar to 165 A degrees up to which energy transfer is appreciable. For the case of transfer to semiconducting carbon nanotubes, apart from the process of transfer to the electronic energy levels within the one electron picture, we also consider the possibility of energy transfer to the lowest possible excitonic state. Transfer to semiconducting carbon nanotubes is possible only if>=epsilon(g)-epsilon(b). The long range behavior of the rate of transfer has been found to have a d(-5) dependence if h >=epsilon(g). But, when the emission energy of the fluorophore is in the range epsilon(g)>h >=epsilon(g)-epsilon(b), the rate has an exponential dependence on the distance. For the case of transfer from pyrene to the semiconducting (6,4) carbon nanotube, energy transfer is found to be appreciable up to a distance of similar to 175 A degrees.

Analysis of Energy Quantization Effects on Single-Electron Transistor Circuits

In this paper, the effects of energy quantization on different single-electron transistor (SET) circuits (logic inverter, current-biased circuits, and hybrid MOS-SET circuits) are analyzed through analytical modeling and Monte Carlo simulations. It is shown that energy quantizationmainly increases the Coulomb blockade area and Coulomb blockade oscillation periodicity, and thus, affects the SET circuit performance. A new model for the noise margin of the SET inverter is proposed, which includes the energy quantization effects. Using the noise margin as a metric, the robustness of the SET inverter is studied against the effects of energy quantization. An analytical expression is developed, which explicitly defines the maximum energy quantization (termed as ``quantization threshold'') that an SET inverter can withstand before its noise margin falls below a specified tolerance level. The effects of energy quantization are further studiedfor the current-biased negative differential resistance (NDR) circuitand hybrid SETMOS circuit. A new model for the conductance of NDR characteristics is also formulated that explains the energy quantization effects.

Impedance studies on high energy Li3+ irradiated PZT thin films

The ferroelectric Pb(Zr0.48Ti0.52)O-3 (PZT) thin films prepared by the pulsed laser deposition technique were studied for their response to high energy lithium ion irradiation through impedance spectroscopy. The Debye peaks, observed in the impedance and modulus plots of irradiatedfilms, shifts towards higher frequencies compared to those of unirradiated films. This is equivalent to the trend observed with increase in temperature in the unirradiated films due to the dielectric relaxation. The irradiated films showed a decrease in the grain resistance compared to the unirradiated films. The activation energy of dielectric relaxation increases from 1.25 eV of unirradiated film to 1.62 eV of irradiated film. The observed modifications in the irradiated film were ascribed to the modifications in the grain structure due to the high value of electronic energy loss.

Fluorescent resonant excitation energy transfer in linear polyenes

We have studied the dynamics of excitation transfer between two conjugated polyene molecules whose intermolecular separation is comparable to the molecular dimensions. We have employed a correlated electron model that includes both the charge-charge, charge-bond, and bond-bond intermolecular electron repulsion integrals. We have shown that the excitation transfer rate varies as inverse square of donor-acceptor separation R-2 rather than as R-6, suggested by the Foumlrster type of dipolar approximation. Our time-evolution study alsom shows that the orientational dependence on excitation transfer at a fixed short donor-acceptor separation cannot be explained by Foumlrster type of dipolar approximation beyond a certain orientational angle of rotation of an acceptor polyene with respect to the donor polyene. The actual excitation transfer rate beyond a certain orientational angle is faster than the Foumlrster type of dipolar approximation rate. We have also studied the excitation transfer process in a pair of push-pull polyenes for different push-pull strengths. We have seen that, depending on the push-pull strength, excitation transfer could occur to other dipole coupled states. Our study also allows for the excitation energy transfer to optically dark states which are excluded by Foumlrster theory since the one-photon transition intensity to these states (from the ground state) is zero.

Metabolism of Plasmodium bergheistar, open: II. 32Pi incorporation into high-energy phosphates

Free parasites of Plasmodium berghei were found to incorporate labeled inorganic phosphate into high-energy phosphates by substrate linked and oxidative hosphorylation. But the parasites also appear to utilize the reserve ATP of the host cells when they are within the host cells which may indicate the dependence of the parasite on the host cells for provision of energy. This investigation formed part of the thesis submitted in 1965 for the doctoral degree at the Indian Institute of Science, Bangalore 12, India, and was supported in part by the Council of Scientific and Industrial Research, India.

Comparative analysis of thermophilic and mesophilic proteins using Protein Energy Networks

Background: Thermophilic proteins sustain themselves and function at higher temperatures. Despite their structural and functional similarities with their mesophilic homologues, they show enhanced stability. Various comparative studies at genomic, protein sequence and structure levels, and experimental works highlight the different factors and dominant interacting forces contributing to this increased stability. Methods: In this comparative structure based study, we have used interaction energies between amino acids, to generate structure networks called as Protein Energy Networks (PENs). These PENs are used to compute network, sub-graph, and node specific parameters. These parameters are then compared between the thermophile-mesophile homologues. Results: The results show an increased number of clusters and low energy cliques in thermophiles as the main contributing factors for their enhanced stability. Further more, we see an increase in the number of hubs in thermophiles. We also observe no community of electrostatic cliques forming in PENs. Conclusion: In this study we were able to take an energy based network approach, to identify the factors responsible for enhanced stability of thermophiles, by comparative analysis. We were able to point out that the sub-graph parameters are the prominent contributing factors. The thermophiles have a better-packed hydrophobic core. We have also discussed how thermophiles, although increasing stability through higher connectivity retains conformational flexibility, from a cliques and communities perspective.

Comparative analysis of thermophilic and mesophilic proteins using Protein Energy Networks

Background: Thermophilic proteins sustain themselves and function at higher temperatures. Despite their structural and functional similarities with their mesophilic homologues, they show enhanced stability. Various comparative studies at genomic, protein sequence and structure levels, and experimental works highlight the different factors and dominant interacting forces contributing to this increased stability. Methods: In this comparative structure based study, we have used interaction energies between amino acids, to generate structure networks called as Protein Energy Networks (PENs). These PENs are used to compute network, sub-graph, and node specific parameters. These parameters are then compared between the thermophile-mesophile homologues. Results: The results show an increased number of clusters and low energy cliques in thermophiles as the main contributing factors for their enhanced stability. Further more, we see an increase in the number of hubs in thermophiles. We also observe no community of electrostatic cliques forming in PENs. Conclusion: In this study we were able to take an energy based network approach, to identify the factors responsible for enhanced stability of thermophiles, by comparative analysis. We were able to point out that the sub-graph parameters are the prominent contributing factors. The thermophiles have a better-packed hydrophobic core. We have also discussed how thermophiles, although increasing stability through higher connectivity retains conformational flexibility, from a cliques and communities perspective.

Studies on the conformation of amino acids XII. Energy calculations on prolyl residue

The favoured conformations of the prolyl residue have been obtained by calculating their potential energies arising from bond-angle strain, torsion-angle strain, non-bonded and electrostatic interatomic energies. In addition to the five membered ring, the peptide unit at the amino end (with ω = 180°) and the C′ atom at the carboxyl end have been taken into account. It is found that there are two local minima in the configurational space of the parameters defining the conformation, as is actually observed-one (denoted by B) with Cγ displaced on the same side as C′, which is lower in energy than the other (denoted by A) with Cγ displaced on the opposite side of C′. The other four atoms Cδ, N, Cα, Cβ are nearly in a plane. The conformations of minimum energy (for both A and B) have bond angles very close to the mean observed values while the torsion angles are well within the range observed in various structures for each type. Taking into account the fact that the influence of neighbouring molecules in a crystal structure may make the conformation of a molecule different from the minimal one, the ranges of the conformational parameters for which the energy is within 0.6 kcal/mole above the minimum value (called the "most probable range") and within 1.2 kcal/mole (called the "probable range") have been determined. The ranges thus obtained, agree well with observation, and most of the observed data lie within the most probable ranges, although differing appreciably from the conformation of minimum energy. The study has been extended, in a limited way, to the conformation of the ring in the amino acid proline. Since the nitrogen is tetrahedral in this (as contrasted with being planar in the prolyl residue), it is found that any one of the five atoms can be out of plane (either way), with the other four lying nearly in a plane. These correspond to low energy conformations (up to 1.2 kcal/mole above the minimum). One such example, in which the Cα atom is out of plane is known for dl-proline · HCl. It is also shown that in these calculations energies due to bond length distortions can be neglected to a good degree of approximation, provided the 'best' values of the bond lengths for the particular compound are used in the theoretical calculations.

Free energy of mixing of divalent basic oxides with silica

An expression derived for the free energy of mixing of a divalent basic oxide (MO) with SiO2 based on a model of silicate structure, takes into account the distribution of O2- (from MO) into the silica network, the mixing of silicate ions with O2- and the enthalpy of mixing. The resulting expression is ΔGmix=RT{N11n (2N1-N)2/4N1(1-N)+N21n N 2-N/1-N}, where N={(β+N1)-√(β+N 1)2-8βN1N2}/2β β=characteristic constant for the system N1=mol fraction of silica N2=mol fraction of MO. For the proper choice of β, calculated values of the activity of MO for the system PbO-SiO2, MnO-SiO2, FeO-SiO2 and CaO-SiO2 are in good agreement with experiment. The model predicts that the activity of the basic oxide decreases with increase in temperature.

Potential functions for hydrogen bond interactions - IV. Minimum Energy Conformation of the α-Helical Structure of PoIy-L-Alanine

Making use of the empirical potential functions for peptide NH .. O bonds, developed in this laboratory, the relative stabilities of the rightand left-handed α-helical structures of poly-L-alanine have been investigated, by calculating their conformational energies (V). The value of Vmin of the right-handed helix (αP) is about - 10.4 kcal/mole, and that of the left-handed helix (αM) is about - 9.6 kcal/mole, showing that the former is lower in energy by 0.8 kcal/mole. The helical parameters of the stable conformation of αP are n ∼ 3.6 and h ∼ 1.5 Å. The hydrogen bond of length 2.85 Å and nonlinearity of about 10° adds about 4.0 kcal/ mole to the stabilising energy of the helix in the minimum enregy region. The energy minimum is not sharply defined, but occurs over a long valley, suggesting that a distribution of conformations (φ{symbol}, ψ) of nearly the same energy may occur for the individual residues in a helix. The experimental data of a-helical fibres of poly-L-alanine are in good agreement with the theoretical results for αP. In the case of proteins, the mean values of (φ{symbol}, ψ) for different helices are distributed, but they invariably occur within the contour for V = Vmin + 2 kcal/mole for αP.

Electron energy equation for an atomic radiating plasma

The electron-energy equation for an atomic radiating plasma is considered in this work. Using the atomic model of Bates, Kingston and McWhirter, the radiation loss-term valid for all optical thicknesses is obtained. A study of the energy gained by electrons in inelastic collisions shows that the radiation loss term can be neglected only for rapidly-decaying or fast-growing plasmas. Emission from optically thin plasmas is considered next and an exact expression is given for the total radiation loss in a recombination continuum. A derivation of the Kramers-Unsöld approximation is presented and the error involved in estimating the total emitted recombination radiation by this approximation is shown to be small.