ProBiS: a web server for detection of structurally similar protein binding sites

A web server, ProBiS, freely available at http://probis.cmm.ki.si, is presented. This provides access to the program ProBiS (Protein Binding Sites), which detects protein binding sites based on local structural alignments. Detailed instructions and user guidelines for use of ProBiS are available at the server under ‘HELP’ and selected examples are provided under ‘EXAMPLES’

Designing an effective climate-policy mix: accounting for instrument synergy

We assess evidence from theoretical-modelling, empirical and experimental studieson how interactions between instruments of climate policy affect overall emissionsreduction. Such interactions take the form of negative, zero or positive synergisticeffects. The considered instruments comprise performance and technical standards,carbon pricing, adoption subsidies, innovation support, and information provision.Based on the findings, we formulate climate-policy packages that avoid negativeand employ positive synergies, and compare their strengths and weaknesses onother criteria. We note that the international context of climate policy has beenneglected in assessments of policy mixes, and argue that transparency andharmonization of national policies may be key to a politically feasible path to meetglobal emissio

Designing an effective climate-policy mix: accounting for instrument synergy

We assess evidence from theoretical-modelling, empirical and experimental studies on how interactions between instruments of climate policy affect overall emissions reduction. Such interactions take the form of negative, zero or positive synergistic effects. The considered instruments comprise performance and technical standards, carbon pricing, adoption subsidies, innovation support, and information provision. Based on the findings, we formulate climate-policy packages that avoid negative and employ positive synergies, and compare their strengths and weaknesses on other criteria. We note that the international context of climate policy has been neglected in assessments of policy mixes, and argue that transparency and harmonization of national policies may be key to a politically feasible path to meet global emission targets. This suggests limiting the complexity of climate-policy packages

Co-dynamics of climate policy stringency and public support

Unidad de excelencia María de Maeztu CEX2019-000940-MAcord transformatiu CRUE-CSICPublic support for stringent climate policies is currently weak. We develop a model to study the dynamics of public support for climate policies. It comprises three interconnected modules: one calculates policy impacts; a second translates these into policy support mediated by social influence; and a third represents the regulator adapting policy stringency depending on public support. The model combines general-equilibrium and agent-based elements and is empirically grounded in a household survey, which allows quantifying policy support as a function of effectiveness, personal wellbeing and distributional effects. We apply our approach to compare two policy instruments, namely carbon taxation and performance standards, and identify intertemporal trajectories that meet the climate target and count on sufficient public support. Our results highlight the importance of social influence, opinion stability and income inequality for public support of climate policies. Our model predicts that carbon taxation consistently generates more public support than standards. Finally, we show that under moderate social influence and income inequality, an increasing carbon tax trajectory combined with progressive revenue redistribution receives the highest average public support over time

Strain Localization in Pyroxenite by Reaction-Enhanced Softening in the Shallow Subcontinental Lithospheric Mantle

We report structural evidence of ductile strain localization in mantle pyroxenite from the spinel to plagioclase websterite transition in the Ronda Peridotite (southern Spain). Mapping shows that, in this domain, small-scale shear zones occurring at the base of the lithospheric section are systematically located within thin pyroxenite layers, suggesting that the pyroxenite was locally weaker than the host peridotite. Strain localization is associated with a sudden decrease of grain size and increasing volume fractions of plagioclase and amphibole as a result of a spinel to plagioclase phase transformation reaction during decompression. This reaction also fostered hydrogen extraction (‘dehydroxylation') from clinopyroxene producing effective fluid saturation that catalyzed the synkinematic net-transfer reaction. This reaction produced fine-grained olivine and plagioclase, allowing the onset of grain-size sensitive creep and further strain localization in these pyroxenite bands. The strain localization in the pyroxenites is thus explained by their more fertile composition, which allowed earlier onset of the phase transition reactions. Geothermobarometry undertaken on compositionally zoned constituent minerals suggests that this positive feedback between reactions and deformation is associated with cooling from at least 1000°C to 700°C and decompression from 1·0 to 0·5 GP

Ultra-high resolution X-ray structure of orthorhombic bovine pancreatic Ribonuclease A at 100K

The crystal structure of orthorhombic Bovine Pancreatic Ribonuclease A has been determined to 0.85 Å resolution using low temperature, 100 K, synchrotron X-ray data collected at 16000 keV (λ = 0.77 Å). This is the first ultra-high-resolution structure of a native form of Ribonuclease A to be reported. Refinement carried out with anisotropic displacement parameters, stereochemical restraints, inclusion of H atoms in calculated positions, five SO2−4 moieties, eleven ethanol molecules and 293 water molecules, converged with final R values of R1(Free) = 0.129 (4279 reflections) and R1 = 0.112 (85,346 reflections). The refined structure was deposited in the Protein Data Bank as structure 7p4r. Conserved waters, using four high resolution structures, have been investigated. Cluster analysis identified clusters of water molecules that are associated with the active site of Bovine Ribonuclease A. Particular attention has been paid to making detailed comparisons between the present structure and other high quality Bovine Pancreatic Ribonuclease A X-ray crystal structures with special reference to the deposited classic monoclinic structure 3RN3 Howlin et al. (Acta Crystallogr A 45:851–861, 1989). Detailed studies of various aspects of hydrogen bonding and conformation have been carried out with particular reference to active site residues Lys-1, Lys-7, Gln-11, His-12, Lys-41, Asn-44, Thr-45, Lys-66, His-119 and Ser-123. For the two histidine residues in the active site the initial electron density map gives a clear confirmation that the position of His-12 is very similar in the orthorhombic structure to that in 3RN3. In 3RN3 His-119 exhibited poor electron density which was modelled and refined as two distinct sites, A (65%) and B (35%) but with respect to His-119 in the present ultra-high resolution orthorhombic structure there is clear electron density which was modelled and refined as a single conformation distinct from either conformation A or B in 3RN3. Other points of interest include Serine-32 which is disordered at the end of the sidechain in the present orthorhombic form but has been modelled as a single form in 3RN3. Lysine-66: there is density indicating a possible conformation for this residue. However, the density is relatively weak, and the conformation is unclear. Three types of amino acid representation in the ultra-high resolution electron density are examined: (i) sharp with very clearly resolved features, for example Lys-37; (ii) well resolved but clearly divided into two conformations which are well behaved in the refinement, both having high quality geometry, for example Tyr-76; (iii) poor density and difficult or impossible to model, an example is Lys-31 for which density is missing except for Cβ. The side chains of Gln-11, His-12, Lys-41, Thr-45 and His-119 are generally recognised as being closely involved in the enzyme activity. It has also been suggested that Lys-7, Asp-44, Lys-66, Phe-120, Asp-121 and Ser-123 may also have possible roles in this mechanism. A molecular dynamics study on both structures has investigated the conformations of His-119 which was modelled as two conformations in 3RN3 but is observed to have a single clearly defined conformation in the present orthorhombic structure. MD has also been used to investigate Lys-31, Lys-41 and Ser32. The form of the Ribonuclease A enzyme used in both the present study and in 3RN3 (Howlin et al. in Acta Crystallogr A 45:851–861, 1989) includes a sulphate anion which occupies approximately the same location as the PO2−4 phosphate group in protein nucleotide complexes (Borkakoti et al. in J Mol Biol 169:743–755, 1983). The present structure contains 5 SO2−4 groups SO41151–SO41155 two of which, SO41152 and SO41153 are disordered, SO41152 being in the active site, and 11 EtOH molecules, EOH A 201–EOH A 211 all of which have good geometry. H atoms were built into the EtOH molecules geometrically. Illustrations of these features in the present structure are included here. The sulphates are presumably present in the material purchased for use in the present study. 293 water molecules are included in the present structure compared to 134 in 3RN3 (Howlin et al. in Acta Crystallogr A 45:851–861, 1989)

The architecture of the European-Mediterranean lithosphere: A synthesis of the Re-Os evidence

Rhenium-depletion model ages (TRD) of sulfi des in peridotite xenoliths from the subcontinental mantle beneath central Spain (the Calatrava volcanic fi eld) reveal that episodes of mantle magmatism and/or metasomatism in the Iberia microplate were linked to crustal growth events, mainly during supercontinent assembly and/or breakup at ca. 1.8, 1.1, 0.9, 0.6, and 0.3 Ga. A synthesis of available in situ and whole-rock Os-isotope data on mantlederived peridotites shows that this type of mantle (maximum TRD of ca. 1.8 Ga) is widespread in the subcontinental mantle of Europe and Africa outboard from the Betics-Maghrebides- Appenines front. In contrast, the mantle enclosed within the Alpine domain records TRD as old as 2.6 Ga, revealing a previously unrecognized Archean domain or domains in the central and western Mediterranean. Our observations indicate that ancient fragments of subcontinental lithospheric mantle have played an important role in the development of the present architecture of the Mediterranean lithosphere

Maximum Cliques in Protein Structure Comparison

Computing the similarity between two protein structures is a crucial task in molecular biology, and has been extensively investigated. Many protein structure comparison methods can be modeled as maximum clique problems in specific k-partite graphs, referred here as alignment graphs. In this paper, we propose a new protein structure comparison method based on internal distances (DAST) which is posed as a maximum clique problem in an alignment graph. We also design an algorithm (ACF) for solving such maximum clique problems. ACF is first applied in the context of VAST, a software largely used in the National Center for Biotechnology Information, and then in the context of DAST. The obtained results on real protein alignment instances show that our algorithm is more than 37000 times faster than the original VAST clique solver which is based on Bron & Kerbosch algorithm. We furthermore compare ACF with one of the fastest clique finder, recently conceived by Ostergard. On a popular benchmark (the Skolnick set) we observe that ACF is about 20 times faster in average than the Ostergard's algorithm

Watching subgraphs to improve efficiency in maximum clique search

This paper describes a new technique referred to as watched subgraphs which improves the performance of BBMC, a leading state of the art exact maximum clique solver (MCP). It is based on watched literals employed by modern SAT solvers for boolean constraint propagation. In efficient SAT algorithms, a list of clauses is kept for each literal (it is said that the clauses watch the literal) so that only those in the list are checked for constraint propagation when a (watched) literal is assigned during search. BBMC encodes vertex sets as bit strings, a bit block representing a subset of vertices (and the corresponding induced subgraph) the size of the CPU register word. The paper proposes to watch two subgraphs of critical sets during MCP search to efficiently compute a number of basic operations. Reported results validate the approach as the size and density of problem instances rise, while achieving comparable performance in the general case