Catalytic pathway, substrate binding and stability in SAICAR synthetase: A structure and molecular dynamics study

The de novo purine biosynthesis is one of the highly conserved pathways among all organisms and is essential for the cell viability. A clear understanding of the enzymes in this pathway would pave way for the development of antimicrobial and anticancer drugs. Phosphoribosylaminoimidazole-succinocar boxamide (SAICAR) synthetase is one of the enzymes in this pathway that catalyzes ATP dependent ligation of carboxyaminoimidazole ribotide (CAIR) with L-aspartate (ASP). Here, we describe eight crystal structures of this enzyme, in C222(1) and H3 space groups, bound to various substrates and substrate mimics from a hyperthermophilic archaea Pyrococcus horikoshii along with molecular dynamics simulations of the structures with substrates. Complexes exhibit minimal deviation from its apo structure. The CAIR binding site displays a preference for pyrimidine nucleotides. In the ADP.TMP-ASP complex, the ASP binds at a position equivalent to that found in Saccharomyces cerevisiae structure (PDB: 2CNU) and thus, clears the ambiguity regarding ASP's position. A possible mode for the inhibition of the enzyme by CTP and UTP, observed earlier in the yeast enzyme, is clearly illustrated in the structures bound to CMP and UMP. The ADP.Mg2+.PO4.CD/MP complex having a phosphate ion between the ATP and CAIR sites strengthens one of the two probable pathways (proposed in Escherichia coli study) of catalytic mechanism and suggests the possibility of a phosphorylation taking place before the ASP's attack on CAIR. Molecular dynamic simulations of this enzyme along with its substrates at 90 degrees C reveal the relative strengths of substrate binding, possible antagonism and the role of Mg2+ ions. (C) 2015 Elsevier Inc. All rights reserved.

Minimization Problems Based on Relative alpha-Entropy I: Forward Projection

Minimization problems with respect to a one-parameter family of generalized relative entropies are studied. These relative entropies, which we term relative alpha-entropies (denoted I-alpha), arise as redundancies under mismatched compression when cumulants of compressed lengths are considered instead of expected compressed lengths. These parametric relative entropies are a generalization of the usual relative entropy (Kullback-Leibler divergence). Just like relative entropy, these relative alpha-entropies behave like squared Euclidean distance and satisfy the Pythagorean property. Minimizers of these relative alpha-entropies on closed and convex sets are shown to exist. Such minimizations generalize the maximum Renyi or Tsallis entropy principle. The minimizing probability distribution (termed forward I-alpha-projection) for a linear family is shown to obey a power-law. Other results in connection with statistical inference, namely subspace transitivity and iterated projections, are also established. In a companion paper, a related minimization problem of interest in robust statistics that leads to a reverse I-alpha-projection is studied.

Minimization Problems Based on Relative alpha-Entropy II: Reverse Projection

In part I of this two-part work, certain minimization problems based on a parametric family of relative entropies (denoted I-alpha) were studied. Such minimizers were called forward I-alpha-projections. Here, a complementary class of minimization problems leading to the so-called reverse I-alpha-projections are studied. Reverse I-alpha-projections, particularly on log-convex or power-law families, are of interest in robust estimation problems (alpha > 1) and in constrained compression settings (alpha < 1). Orthogonality of the power-law family with an associated linear family is first established and is then exploited to turn a reverse I-alpha-projection into a forward I-alpha-projection. The transformed problem is a simpler quasi-convex minimization subject to linear constraints.

Relative stabilities of condensed face sharing mono- and di-carboranes: CB20H18 and C2B19H18+

The relative energies of triangular face sharing condensed macro polyhedral carboranes: CB20H18 and C2B19H18+ derived from mono- and di-substitution of carbons in (4) B21H18- is calculated at B3LYP/6-31G* level. The relative energies, H center dot center dot center dot H non-bonding distances, NICS values, topological charge analysis and orbital overlap compatibility connotes the face sharing condensed macro polyhedral mono-carboranes, 8 (4-CB20H18) to be the lowest energy isomer. The di-carba- derivative, (36) 4,4'a-C2B19H18+ with carbons substituted in a different B-12 cage in (4) B21H18- in anti-fashion is the most stable isomer among 28 possibilities. This structure has less non-bonding H center dot center dot center dot H interaction and is in agreement with orbital-overlap compatibility, and these two have the pivotal role in deciding the stability of these clusters. An estimate of the inherent stability of these carboranes is made using near-isodesmic equations which show that CB20H18 (8) is in the realm of the possible. (C) 2015 Elsevier B.V. All rights reserved.

Fuzzy Approach to Rank Global Climate Models

Eleven coupled model intercomparison project 3 based global climate models are evaluated for the case study of Upper Malaprabha catchment, India for precipitation rate. Correlation coefficient, normalised root mean square deviation, and skill score are considered as performance indicators for evaluation in fuzzy environment and assumed to have equal impact on the global climate models. Fuzzy technique for order preference by similarity to an ideal solution is used to rank global climate models. Top three positions are occupied by MIROC3, GFDL2.1 and GISS with relative closeness of 0.7867, 0.7070, and 0.7068. IPSL-CM4, NCAR-PCMI occupied the tenth and eleventh positions with relative closeness of 0.4959 and 0.4562.

Optimized Group Velocity Control Scheme and DNS of Decaying Compressible Turbulence of Relative High Turbulent Mach Number

To overcome the difficulty in the DNS of compressible turbulence at high turbulent Mach number, a new difference scheme called GVC8 is developed. We have succeeded in the direct numerical simulation of decaying compressible turbulence up to turbulent Mach number 0.95. The statistical quantities thus obtained at lower turbulent Mach number agree well with those from previous authors with the same initial conditions, but they are limited to simulate at lower turbulent Mach numbers due to the so-called start-up problem. The energy spectrum and coherent structure of compressible turbulent flow are analysed. The scaling law of compressible turbulence is studied. The computed results indicate that the extended self-similarity holds in decaying compressible turbulence despite the occurrence of shocklets, and compressibility has little effects on relative scaling exponents when turbulent Mach number is not very high.

3D simulation of the micro indentation process and relative problems research

In this paper the finite element method was used to simulate micro-scale indentation process. The several standard indenters were simulated with 3D finite element model. The emphasis of this paper was the differences between 2D axisymmetric cone model and

Comparison of relative flexoelectric coefficients measured by different techniques

While it is well known that it is possible to determine the effective flexoelectric coefficient of nematic liquid crystals using hybrid cells [1], this technique can be difficult due to the necessity of using a D.C. field. We have used a second method[2], requiring an A.C. field, to determine this parameter and here we compare the two techniques. The A.C. method employs the linear flexoelectrically induced linear electro-optic switching mechanism observed in chiral nematics. In order to use this second technique a chiral nematic phase is induced in an achiral nematic by the addition of a small amount of chiral additive (∼3% concentration w/w) to give helix pitch lengths of typically 0.5-1.0 μm. We note that the two methods can be used interchangeably, since they produce similar results, and we conclude with a discussion of their relative merits.

Analysis of Spacecraft Relative Motion and Applicability of Hill's Solution

研究了空间飞行器编队中最具基础性的问题之一,即相对运动的解析表达及Hill方程的适用条件。通过建立相对运动的通解公式,针对不同性质的初值深入地分析了其相对运动轨迹的本质特征,并给出了Hill方程的适用条件。此外,文中还给出了一个新的编队设计简化公式。

Assessing the relative road damaging potential of HGVs

Assessing the road damaging potential of heavy vehicles is becoming an increasingly important issue. In this paper, current vehicle regulations and possible future alternatives are reviewed, and are categorized as tests on individual axles and whole vehicles, and 'direct' and 'indirect' tests. Whole vehicle methods of assessing road damaging potential accurately are then discussed. Direct methods are investigated (focussing on using a force measuring mat), and drawbacks are highlighted. Indirect methods using a transient input applied to individual axles are then examined. Results indicate that if non-linearities are accounted for properly, indirect methods of assessing whole vehicle road damaging potential could offer the required accuracy for a possible future test procedure.

Individual notions of distributive justice and relative economic status

We present two experiments designed to investigate whether individuals’ notions of distributive justice are associated with their relative (within-society) economic status. Each participant played a specially designed four-person dictator game under one of two treatments, under one initial endowments were earned, under the other they were randomly assigned. The first experiment was conducted in Oxford, United Kingdom, the second in Cape Town, South Africa. In both locations we found that relatively well-off individuals make allocations to others that reflect those others’ initial endowments more when those endowments were earned rather than random; among relatively poor individuals this was not the case.

Relative tolerance of mat-forming algae to copper

This study documents the relative tolerance of the common, weedy mat-forming green algae Hydrodictyon , Oedogonium , Pithophora , Rhizoclonium , and Spirogyra to copper. In addition, the copper tolerance of the cyanobacterial (blue-green algal) mat-forming Oscillatoria was assessed.