Coupled folding-binding versus docking: a lattice model study

Using a simple hydrophobic/polar protein model, we perform a Monte Carlo study of the thermodynamics and kinetics of binding to a target structure for two closely related sequences, one of which has a unique folded state while the other is unstructured. We obtain significant differences in their binding behavior. The stable sequence has rigid docking as its preferred binding mode, while the unstructured chain tends to first attach to the target and then fold. The free-energy profiles associated with these two binding modes are compared.     

Molecular simulation of the reversible mechanical unfolding of proteins

In this work we have combined a Wang-Landau sampling scheme [F. Wang and D. Landau, Phys. Rev. Lett. 86, 2050 (2001)] with an expanded ensemble formalism to yield a simple and powerful method for computing potentials of mean force. The new method is implemented to investigate the mechanical deformation of proteins. Comparisons are made with analytical results for simple model systems such as harmonic springs and Rouse chains. The method is then illustrated on a model 15-residue alanine molecule in an implicit solvent. Results for mechanical unfolding of this oligopeptide are compared to those of steered molecular dynamics calculations.     

Alkyne hydroamination triggered cyclizations: A powerful tool for the construction of biologically important structural motifs

This review focuses mainly on recent endeavors in the field of cyclizations triggered by the catalytic hydroamination (formal or direct) of alkynes. The new strategies developed offer an efficient and convenient entry to several heterocycles of biological importance.     

Lipase activity of Lecitase® Ultra: characterization and applications in enantioselective reactions

The general properties of Lecitase® Ultra, a phospholipase manufactured and marketed by Novozymes, Denmark, have been studied after purification by ultrafiltration. The enzyme has a molecular mass of 35 KD, pH-optimum of 8.5, and appears to possess a single active site which exhibits both the lipase and phospholipase activities that increase in the presence of Ca²⁺ and Mg²⁺ ions. The enzyme is inhibited by heavy metal ions and surfactants, and does not accept p-nitrophenyl acetate and glycerol triacetate. Substrates, such as glycerol tributyrate and p-nitrophenyl palmitate, esters of N-acetyl-α-amino acids and α-hydroxy acids are readily accepted. Amino acids with aliphatic residues, such as alanine, isoleucine, and methionine, are hydrolyzed with high enantioselectivity for the l-enantiomer (E >100), but amino acids with aromatic residues such as phenylalanine and phenylglycine, and esters of α-hydroxy acids are hydrolyzed with low enantioselectivity (E = 1–5). Immobilization of the enzyme in a gelatin matrix (gelozyme) leads to a marginal improvement in the enantioselectivity for these substrates. However, a dramatic improvement in enantioselectivity is observed for ethyl 2-hydroxy-4-oxo-4-phenylbutyrate (E value increases from 4.5 to 19.5 with S-selectivity). Similarly, glycidate esters, such as ethyl trans-(±)-3-phenyl glycidate and methyl trans-(±)-3-(4-methoxyphenyl) glycidate, are selectively hydrolyzed with a remarkable selectivity towards the (2S,3R)-enantiomer providing unreacted (2R,3S)-glycidate esters (ee >99%, conversion 52–55%) by the immobilized enzyme.     

Generation of zonal magnetic fields by drift waves in a current carrying nonuniform magnetoplasma

It is shown that zonal magnetic fields (ZMFs) can be nonlinearly excited by incoherent drift waves (DWs) in a current carrying nonuniform magnetoplasma. The dynamics of incoherent DWs in the presence of ZMFs is governed by a wave-kinetic equation. The governing equation for ZMFs in the presence of nonlinear advection force of the DWs is obtained from the parallel component of the electron momentum equation and the Faraday law. Standard techniques are used to derive a nonlinear dispersion relation, which depicts instability via which ZMFs are excited in plasmas. ZMFs may inhibit the turbulent cross-field particle and energy transport in a nonuniform magnetoplasma.     

Chemo-enzymatic synthesis of both enantiomers of rugulactone

The synthesis of both the (R)- and (S)-enantiomers of the natural product rugulactone has been achieved. Candida rugosa lipase hydrolyzes the butyrate ester of the protected 3-hydroxy homoallylic alcohol with very high enantioselectivity (E = 244) and provides the key intermediates with high enantiomeric purity (ee 98–99%) and excellent yields.     

Asymmetric synthesis of Goniothalesdiol A from (R)-2,3-O-cyclohexylidine glyceraldehyde

Goniothalesdiol A 1 has been synthesized from (R)-2,3-O-cyclohexylidine glyceraldehyde with high stereoselectivity and 22% overall yield in 11 simple steps. The key features of the synthetic strategy include the stereocontrolled allylation of (R)-2,3-O-cyclohexylidine glyceraldehydes; the cross-metathesis with a Grubbs’s second generation catalyst, and the intramolecular base-catalyzed oxy-Michael addition for the formation of the tetrahydropyran ring.     

Scope for Exploitation of Consumers Through Speculation: A Dynamic- Programming Approach to the Case of the Indian Sugar Industry

The Government of India (G.O.I.) controls the quantity of sugar released into the domestic market on a monthly basis. This forms a part of the package of public policies affecting the development of the Indian sugar industry, which includes protection from foreign competition, simultaneous existence of an open market for sugar and distribution of sugar at subsidized prices to consumers through the public distribution system (P.D.S.), minimum support prices for the farmers producing sugar-cane, and differential prices paid to sugar factories for the sugar taken over by G.O.I. for the P.D.S.Using a dynamic-programming approach, this paper describes a worst case analysis of the scope for the traders to exploit the consumers under the current policy of controls over releases into the domestic market. The results show the marginal importance of such controls in saving the consumers from the exploitation by traders. Secondly, on the basis of wider research done by the authors, it is concluded that the scope provided to the traders for the exploitation of consumers through the other policies of the package is of such a magnitude as to make the controls over the releases into the market a relatively insignificant policy intervention for protecting the consumers.     

Laser induced optoacoustic spectroscopy of benzil: Evaluation of structural volume change upon photoisomerization

The cis-skew to trans-planar photoisomerization of benzil in the photoexcited state was studied by laser-induced optoacoustic spectroscopy (LIOAS) in a series of normal alkane solvents at room temperature. The structural volume change due to the photoisomerization process has been estimated and compared with the same calculated from the optimized skew and trans structures. The magnitude of the structural volume change is estimated to be 22.9 ± 1.2 mL/mol. This study reveals that an expansion in volume occurs during the photoinduced isomerization process. In non-polar alkane solvents, the estimated volume change has been argued to be free from electrostrictional contribution.