Camdas: An automated conformational analysis system using molecular dynamics

We present an automated conformational analysis program, CAMDAS (Conformational Analyzer with Molecular Dynamics And Sampling). CAMDAS performs molecular dynamics (MD) calculations for a target molecule and samples conformers from the trajectory of the MD. The program then evaluates the similarities between each of the sampled conformers in terms of the root- mean-square deviations of the atomic positions, clusters similar conformers, and finally prints out the clustered conformers. This MD-based conformational analysis is a broadly used method, and CAMDAS is intended to provide a convenient framework for the method. CAMDAS has the ability to find the representative conformers automatically from an arbitrarily given structure of the molecule. The accuracy of the program was examined using N- acetylalanine-N-methylamide, and the obtained result was consistent with that of the systematic search method. In the test calculation of cyclodecane, CAMDAS could identify most of the known conformers and their conformational enantiomers by examining only 5000 conformers. In addition, the potential-scaled method, which we have developed previously as an accelerating technique for MD, could find two additional conformers of cyclodecane that have not been reported. CAMDAS presents a convenient way to find the energetically possible conformers of a molecule, which is needed especially in the early stage of drug design.     

Reaction of 2-methoxy-3H-azepine with NBS: efficient synthesis of 2-substituted 2H-azepines

[reaction: see text] The reaction of 2-methoxy-3H-azepines, in the presence or absence of a nucleophile, with N-bromosuccinimide (NBS) gave a regioselective 1,4-adduct from which the corresponding 2H-azepine derivatives were formed via base-promoted hydrogen bromide elimination, generally in moderate to quantitative yield. Competitive formation of 4-bromo-2-methoxy-3H-azepine by electrophilic substitutuion or 3H-azepin-2-yl 2H-azepin-2-yl ether by transetherification was minimized at lower reaction temperatures. Quantitative substitution of 2-(2',4',6'-trichlorophenoxy)-2H-azepine derivatives, formed in moderate yield from the respective 3H-azepine and NBS in the presence of 2,4,6-trichlorophenol (TCP), by various nucleophiles gave the corresponding 2-substituted 2H-azepine. Among these nucleophiles were alkanethiol and alkylamine that are not tolerated in the reaction of 3H-azepine and NBS.     

Enantioselective Morita–Baylis–Hillman reaction catalyzed by a chiral phosphine oxide

An application of a hypervalent silicon complex, generated from a chiral phosphine oxide catalyst and silicon tetrachloride, to the enantioselective organocatalytic Morita–Baylis–Hillman reaction is described. A chloride anion liberated from the hypervalent silicon complex smoothly generated a γ-chloro silyl enol ether that subsequently reacted with an aldehyde to afford the Baylis–Hillman adducts in good yields and with good enantioselectivities.     

Identification of novel EED-EZH2 PPI inhibitors using an in silico fragment mapping method

Journal of Computer-Aided Molecular Design - Enhancer of zeste homolog 2 (EZH2) is a histone lysine methyltransferase that is overexpressed in many cancers. Numerous EZH2 inhibitors have been...     

Efficient direct electron transfer with enzyme on a nanostructured carbon film fabricated with a maskless top-down UV/ozone process

We have developed a new carbon film electrode material with thornlike surface nanostructures to realize efficient direct electron transfer (DET) with enzymes, which is very important for various enzyme biosensors and for anodes or cathodes used in biofuel cells. The nanostructures were fabricated using UV/ozone treatment without a mask, and the obtained nanostructures were typically 2-3.5 nm high as confirmed by atomic force microscopy measurements. X-ray photoelectron spectroscopy and transmission electron microscopy revealed that these nanostructures could be formed by employing significantly different etching rates depending on nanometer-order differences in the local sp(3) content of the nanocarbon film, which we fabricated with the electron cyclotron resonance sputtering method. These structures could not be realized using other carbon films such as boron-doped diamond, glassy carbon, pyrolyzed polymers based on spin-coated polyimide or vacuum-deposited phthalocyanine films, or diamond-like carbon films because those carbon films have relatively homogeneous structures or micrometer-order crystalline structures. With physically adsorbed bilirubin oxidase on the nanostructured carbon surface, the DET catalytic current amplification was 30 times greater than that obtained with the original carbon film with a flat surface. This efficient DET of an enzyme could not be achieved by changing the hydrophilicity of the flat carbon surface, suggesting that DET was accelerated by the formation of nanostructures with a hydrophilic surface. Efficient DET was also observed using cytochrome c.     

A normalization method of input data that conserves the norm information for competitive learning neural network using inner product

Normalization of input vector is essential for a competitive learning neural network using the inner product. In this paper we propose a transformation method of input vector without losing the norm information. To conserve the norm information, an additional vector component concerning the norm is introduced besides the original normalized components of the input vector. By applying the method to Kohonen’s self-organizing feature map, its usefulness is demonstrated. We also propose an optical apparatus for its realization.     

Prospective trial of a navigator setting under left hepatic lobe on magnetic resonance cholangiopancreatography using a free-breathing prospective acquisition correction technique

PURPOSE: To prospectively compare the image acquisition time and image quality obtained by navigator setting under the left hepatic lobe vs. on the right diaphragm on magnetic resonance cholangiopancreatography (MRCP) using a free-breathing navigator-triggered prospective acquisition correction technique (PACE). MATERIALS AND METHODS: Fifty consecutive patients prospectively underwent three-dimensional T2-weighted turbo spin-echo MRCP using PACE with the navigator randomly set either under the left hepatic lobe or on top of the right diaphragm. Image acquisition time and subjective image quality were compared on a five-point scale using Student's t-test and Mann-Whitney's U test, respectively. RESULTS: There was no significant difference for mean acquisition time (6.1+/-1.6 vs. 6.3+/-1.2 min, P=.689) between the left hepatic lobe group and right diaphragm group. Mean subjective image quality was significantly worse in the left hepatic lobe group than in the right diaphragm group (4.1 vs. 4.7, P=.044). CONCLUSION: Setting the navigator under the left hepatic lobe for MRCP using PACE causes the data processing to be more difficult. As well, under current circumstances, it does not contribute to reducing acquisition time or improving the image quality.     

Lariatins, antimycobacterial peptides produced by Rhodococcus sp. K01-B0171, have a lasso structure

Two antimycobacterial agents, lariatins A and B, were isolated from the culture broth of Rhodococcus sp. K01-B0171. Their structures were elucidated by spectral analysis and advanced protein chemical methods to be unique cyclic peptides, which consist of 18 and 20 L-amino acid residues with an internal linkage between the gamma-carboxyl group of Glu8 and the alpha-amino group of Gly1. The three-dimensional structure of lariatin A deduced from NMR data by dynamical simulated annealing method indicates that the tail segment (Trp9-Pro18) passes through the ring segment (Gly1-Glu8) to form a 'lasso' structure.