Steric factors override thermodynamic driving force in regioselectivity of proline hydroxylation by prolyl-4-hydroxylase enzymes

Prolyl-4-hydroxylase is an important nonheme iron-containing dioxygenase in humans involved in the regioselective hydroxylation of a proline residue in a peptide chain on the C(4) position. In biosystems this process is important to create collagen cross-linking and cellular responses to hypoxia. We have performed a series of density functional theory (DFT) studies into the origin of the regioselectivity of proline hydroxylation by P4H enzymes using a minimal active site model (where substrate is unhindered in the binding site) and a larger active site model that incorporates steric hindrance of the substrate by several secondary sphere aromatic residues. Our studies show that thermodynamically the most favorable hydrogen atom abstraction position of proline is from the C(5) position; hence, the small model gives a low reaction barrier and large exothermicity for this process. However, stereochemical repulsions of the substrate with aromatic residues of Tyr(140) and Trp(243) in the second coordination sphere prevent C(5) hydroxylation and make C(4) hydroxylation the dominant mechanism, despite a lesser driving force for the reaction. These studies explain the remarkable regioselectivity of proline hydroxylation by P4H enzymes and show that the regioselectivity is kinetically controlled but not thermodynamically. In addition, we calculated spectroscopic parameters and found good agreement with experimental data.     

Selection of aptamers for signal transduction proteins by capillary electrophoresis

High‐affinity aptamers for important signal transduction proteins, i.e. Cdc42‐GTP, p21‐activated kinase1 (PAK1) and MRCK (myotonic dystrophy kinase‐related Cdc42‐binding kinase) α were successfully selected in the low micro‐ to nanomolar range using non‐systematic evolution of ligands by exponential enrichment (SELEX) with at least three orders of magnitude enhancement from their respective bulk affinity of naïve DNA library. In the non‐SELEX procedure, CE was used as a highly efficient affinity method to select aptamers for the desired molecular target through a process that involved repetitive steps of partitioning, known as non‐equilibrium CE of equilibrium mixtures with no PCR amplification between successive steps. Various non‐SELEX conditions including the type, concentration and pH of the run buffer were optimized. Other considerations such as salt composition of selection buffer, protein concentration and sample injection size were also studied for high stringency during selection. After identifying the best enriched aptamer pool, randomly selected clones from the aptamer pool were sequenced to obtain the individual DNA sequences. The dissociation constants (K_d) of these sequences were in the low micromolar to nanomolar range, indicating high affinity to the respective proteins. The best binders were also subjected to sequence alignment to generate a phylogenetic tree. No significant consensus region based on approximately 50 sequences for each protein was observed, suggesting the high efficiency of non‐SELEX for the selection of numerous unique sequences with high selectivity.     

Fate of the resonating valence bond in graphene

We apply a variational wave function capable of describing qualitatively and quantitatively the so-called "resonating valence bond" (RVB) in realistic materials, by improving standard ab initio calculations by means of quantum Monte Carlo methods. In this framework we clearly identify the Kekulé and Dewar contributions to the chemical bond of the benzene molecule and establish the corresponding RVB energy of these structures (?0.01 eV/atom). We apply this method to unveil the nature of the chemical bond in undoped graphene, providing an estimate of the RVB energy gain, and show that this picture remains only within a small "resonance length" of a few atomic units.     

Affleck-Kennedy-Lieb-Tasaki state on a honeycomb lattice is a universal quantum computational resource

Universal quantum computation can be achieved by simply performing single-qubit measurements on a highly entangled resource state, such as cluster states. The family of Affleck-Kennedy-Lieb-Tasaki states has recently been intensively explored and shown to provide restricted computation. Here, we show that the two-dimensional Affleck-Kennedy-Lieb-Tasaki state on a honeycomb lattice is a universal resource for measurement-based quantum computation.     

11B and constraints on neutrino oscillations and spectra from neutrino nucleosynthesis

We study the sensitivity to variations in the triple-alpha and 12C(α,γ)16O reaction rates, of the yield of the neutrino-process isotopes 7Li, 11B, 19F, 138La, and 180Ta in core-collapse supernovae. Compared to solar abundances, less than 15% of 7Li, about 25%-80% of 19F, and about half of 138La is produced in these stars. Over a range of ±2σ for each helium-burning rate, 11B is overproduced and the yield varies by an amount larger than the variation caused by the effects of neutrino oscillations. The total 11B yield, however, may eventually provide constraints on supernova neutrino spectra.     

Best Fourier Approximation and Application in Efficient Blurred Signal Reconstruction

We expand upon the known results on sharp linear Fourier methods of approximation where the approximation is the best in terms of both rate and constant among all polynomial procedures of approximation. So far these results have been studied due to their mathematical beauty rather than their practical importance. In this paper we show that they are the core mathematics underlying best statistical methods of solving noisy ill-posed problems. In particular, we suggest a procedure for recovery of noisy blurred signals based on samples of small sizes where a traditional statistics concludes that the complexity of such a setting makes the problem not worthy of a further study. Thus, we present a problem where a combination of the classical approximation theory and statistics leads to interesting practical results.     

Integrating across Pascal's triangle

Sums across the rows of Pascal's triangle yield n² while certain diagonal sums yield the Fibonacci numbers which are asymptotic to ?n where ? is the golden ratio. Sums across other diagonals yield quantities asymptotic to cn where c depends on the directions of the diagonals. We generalize this to the continuous case. Using the gamma function, we generalize the binomial coefficients to real variables and thus form a generalization of Pascal's triangle. Integration over various families of lines and curves yields quantities asymptotic to cx where c is determined by the family and x is a parameter. Finally, we revisit the discrete case to get results on sums along curves.