Crowding alters the folding kinetics of a β-hairpin by modulating the stability of intermediates

Crowded environments inside cells exert significant effects on protein structure, stability, and function, but their effects on (pre)folding dynamics and kinetics, especially at molecular levels, remain ill-understood. Here, we examine the latter for, as an initial candidate, a small de novo β-hairpin using extensive all-atom molecular dynamics simulations for crowder volume fractions φ up to 40%. We find that crowding does not introduce new folding intermediates or misfolded structures, although, as expected, it promotes compact structures and reduces the accessible conformational space. Furthermore, while hydrophobic-collapse-mediated folding is slightly enhanced, the turn-directed zipper mechanism (dominant in crowder-free situations) increases many-fold, becoming even more dominant. Interestingly, φ influences the stability of the folding intermediates (FI(1) and FI(2)) in an apparently counterintuitive manner, which can be understood only by considering specific intrachain interactions and intermediate (and hierarchical) structural transitions. For φ values <20%, native-turn formation is enhanced, and FI(1), characterized by a hairpin structure but slightly mismatched hydrophobic contacts, increases in frequency, thus enhancing eventual folding. However, higher φ values impede native-turn formation, and FI(2), which lacks native turns, re-emerges and increasingly acts as a kinetic trap. The change in the stability of these intermediates with φ strongly correlates with the hierarchical folding stages and their kinetics. The results show that crowding assists intermediate structural changes more by impeding backward transitions than by promoting forward transitions and that a delicate competition between reduction in configuration space and introduction of kinetic traps along the folding route is key to understanding folding kinetics under crowded conditions.     

The structure of states and maps in quantum theory

The structure of statistical state spaces in the classical and quantum theories are compared in an interesting and novel manner. Quantum state spaces and maps on them have rich convex structures arising from the superposition principle and consequent entanglement. Communication channels (physical processes) in the quantum scheme of things are in one-to-one correspondence with completely positive maps. Positive maps which are not completely positive do not correspond to physical processes. Nevertheless they prove to be invaluable mathematical tools in establishing or witnessing entanglement of mixed states. We consider some of the recent developments in our understanding of the convex structure of states and maps in quantum theory, particularly in the context of quantum information theory.     

Stochastic resonance and energy optimization in spatially extended dynamical systems

We investigate a class of nonlinear wave equations subject to periodic forcing and noise, and address the issue of energy optimization. Numerically, we use a pseudo-spectral method to solve the nonlinear stochastic partial differential equation and compute the energy of the system as a function of the driving amplitude in the presence of noise. In the fairly general setting where the system possesses two coexisting states, one with low and another with high energy, noise can induce intermittent switchings between the two states. A striking finding is that, for fixed noise, the system energy can be optimized by the driving in a form of resonance. The phenomenon can be explained by the Langevin dynamics of particle motion in a double-well potential system with symmetry breaking. The finding can have applications to small-size devices such as microelectromechanical resonators and to waves in fluid and plasma.     

Electronic topological transition and phase transition in rhodium and iridium based inter metallic compounds

Of the Rh₃Y, Rh₃La, Ir₃Y and Ir₃La inter-metallic compounds, the compound Rh₃Y exists in hexagonal structure, Ir₃Y and Ir₃La exist in rhombohedral structure, whereas the compound Rh₃La exists in both hexagonal and rhombohedral structures. Based on our tight binding-linear muffin tin orbital (TB-LMTO) study of other rhodium and iridium-based Rh₃X and Ir₃X (where X=Ti, Zr, Hf, V, Nb, Ta and Sc) inter-metallic compounds of AuCu₃ type cubic structure, an attempt is made to examine whether the compounds Rh₃Y, Rh₃La, Ir₃Y and Ir₃La will undergo a structural phase transition to cubic structure from their experimentally reported structures. From our study, it is observed that the compounds Rh₃Y and Rh₃La undergo a structural phase transition to cubic phase at 4.5 and 10.1 GPa, respectively, from their experimentally reported hexagonal and rhombohedral phases. Further it is predicted that both the compounds Ir₃Y and Ir₃La can exist in the cubic phase itself at ambient condition, in contrary to the experimental observation. From the band structure outputs that have been plotted for the compounds under compression, it is observed that the compounds Rh₃La, Ir₃Y and Ir₃La undergo the Lifshitz type of transition which may change the Fermi surface topology and hence the physical properties of these compounds.     

Enhanced sensitivity for the differential pulse polarographic determination of Mo(VI) based on adsorption catalytic current

A differential pulse polarographic (DPP) method based on the adsorption catalytic current in a medium containing chlorate and 8-hydroxyquinoline (oxine) is suggested for the determination of molybdenum(VI). Experimental conditions such as pH and the composition of supporting electrolyte have been optimized to get a linear calibration graph at trace levels of Mo(VI). The sensitivity for molybdenum can be considerably enhanced by this method. The influence of possible interferences on the catalytic current has been investigated. The sensitivity of the method is compared with those obtained for other DPP methods for molybdenum. A detection limit of 1.0 × 10^–8 mol/L has been found.     

Characterization of the dimeric one-electron electrolytic reduction products of 1-alkylpyridinium ions in acetonitrile

A chemical-electrochemical approach for the determination of the positions of coupling in the dimeric one-electron reduction products of 1-alkylpyridinium ions in acetonitrile is described. The procedure involves the treatment of a solution of the dimeric species with an appropriate quinone followed by electrochemical examination of the resulting solution. For 1-alkylpyridinium ions without ring substituents, the dimer is concluded to be the 4,4′ coupled isomer, based on the formation in the cases of 1-methyl-, 1-ethyl-, and 1-benzylpyridinium ions of the 1,1′-dialkyl-4,4′-bipyridinium monocation radical species on treatment of the dimeric species with 1,4-benzoquinone. The characteristics, particularly the quantitative nature, of this tetrahydrobipyridine-quinone reaction have been examined.     

Left-handed and ambidextrous helices in the gas phase

We have used ion mobility mass spectrometry to study the effect of d-residues on helix formation in unsolvated alanine-based peptides. The right-handed helix of AC-A15K + H+ is significantly disrupted when five or more of the natural L-residues are randomly replaced with D-residues. On the other hand, when a block of L-residues is replaced with D-residues, an unusual ambidextrous structure with helical segments of opposite chirality is formed. A peptide with all D-residues forms a left-handed helix.     

Base catalyzed rearrangement of oxy-cope systems

The synthesis and rearrangement of the optically active etynyl and vinyl carbinols 3 and 4 are reported. The rearrangements are found to be concerted when carried out with KH-THF and non-concerted with KOH-methanol.     

Instrumentation for charging current compensation in d.c. polarography

It is shown that the non-linear charging current in d.c. polarography can be fairly well compensated by a method (suggested by Barker), which consists in applying a small a.c. voltage to the polarographic cell, rectifying the a.c. response, integrating it and subtracting a suitable fraction from the total d.c. response. An instrument incorporating such an automatic compensation for the nonlinear charging current is described. Results obtained with this instrument are presented to show that the limit of measureable concentrations is about 10^?7M for reversible waves and the precision is ±2.5 to ±3.0%. It is possible to obtain, with the instrument described here, well defined polarograms even when the supporting electrolyte concentration is low.     

A transannular reaction during lithium ammonia reduction of an α,β-unsaturated ketone

The lithium-ammonia reduction of the α,β-unsaturated bicyclic dione 2-methyl-Δ^1,6-bicyclo[6,4,0]cyclododecene-5,9-dione 1 has been found to give two isomeric products 2α-methyl-5-oxo-6β-tricyclo[6,4,0,0^1,9] dodecan-9α-ol 2 and 2-β-methyl-5-oxo-6β-tricyclo[6,4,0,0^1,9]dodecan-9α-ol 3 involving a transannular reaction. Chemical and spectral evidence are presented to support the assigned structures. The stereochemistry of 2 arid 3 is also discussed.