Modified AutoDock for accurate docking of protein kinase inhibitors

Protein kinases are an important class of enzymes controlling virtually all cellular signaling pathways. Consequently, selective inhibitors of protein kinases have attracted significant interest as potential new drugs for many diseases. Computational methods, including molecular docking, have increasingly been used in the inhibitor design process [1]. We have considered several docking packages in order to strengthen our kinase inhibitor work with computational capabilities. In our experience, AutoDock offered a reasonable combination of accuracy and speed, as opposed to methods that specialize either in fast database searches or detailed and computationally intensive calculations.However, AutoDock did not perform well in cases where extensive hydrophobic contacts were involved, such as docking of SB203580 to its target protein kinase p38. Another shortcoming was a hydrogen bonding energy function, which underestimated the attraction component and, thus, did not allow for sufficiently accurate modeling of the key hydrogen bonds in the kinase-inhibitor complexes.We have modified the parameter set used to model hydrogen bonds, which increased the accuracy of AutoDock and appeared to be generally applicable to many kinase-inhibitor pairs without customization. Binding to largely hydrophobic sites, such as the active site of p38, was significantly improved by introducing a correction factor selectively affecting only carbon and hydrogen energy grids, thus, providing an effective, although approximate, treatment of solvation.     

A monopole mass filter with a hyperbolic V-shaped electrode

In this article we compare the classical monopole mass filter of von Zahn and the monopole mass filter with a hyperbolic V-shaped electrode. The experimental results and those of computer simulation for both mass spectrometers are presented. We show that the replacement of a conventional 90 degrees V-shaped electrode by an electrode with a hyperbolic profile substantially improves the peak shape of any given mass, and increases the mass resolution by a factor of 3-4 and the abundance sensitivity by a factor of 100. The potential of high analytical performance combined with electroforming techniques for electrode manufacture indicate future practical uses of such instruments. Copyright 1999 John Wiley & Sons, Ltd.     

Determination of 13C/12C Isotope Ratio in Alcohols of Different Origin by 1н Nuclei NMR-Spectroscopy

Russian Physics Journal - A new express method of indirect assessment of 13C/12C isotope ratio on 1H nuclei is developed to verify the authenticity of ethanol origin in alcohol-water-based fluids...     

Some structural peculiarities of formamide-water binary mixtures according to proton spin-spin relaxation data

The formamide-water system has been studied by the proton spin-spin relaxation method. The compositions of the resulting heterosolvates have been determined along with the stability constants on the mole fraction scale, and the relaxation efficiency coefficients.Original Russian Text Copyright © 2004 by I. V. Sukhno, V. Yu. Buzko, V. T. Panyushkin, and I. A. KovalevaTranslated from Zhurnal Strukturnoi Khimii, Vol. 45, No. 4, pp. 748–750, July–August, 2004.This revised version was published online in April 2005 with a corrected cover date.     

DFT study of the structural characteristics of the yttrium(3+) aqua ion

Density functional theory (DFT) using SVWN5, B3LYP, B3P86, O3LYP, B3PW91, B1LYP, B971, MPW1PW91, PBE1PBE, BHandH, and BHandHLYP density functionals was employed to study the structural characteristics of the Y(H₂O) ₈ ³⁺ yttrium aqua ion. The nonlocal hybrid GGA functionals show worse predictive ability in structural calculations of the Y(H₂O) ₈ ³⁺ aqua ion compared to the relatively simple combined functional BHandH and to the simplest SVWN5 functional in LSDA theory.     

Justification of the Kirchhoff hypotheses and error estimation for two-dimensional models of anisotropic and inhomogeneous plates, including laminated plates

Asymptotic analysis of the problem describing deformation ofa thin cylindrical plate with clamped lateral side is performed.The problem is considered under the most general statement withthe plate being laminated and consisting of an arbitrary numberof nonhomogeneous and anisotropic (21 elastic moduli) layers.Explicit integral representations of the differential operatorswhich form the two-dimensional model of the plate are derived.In the case when the elastic moduli of each of the layers areconstant, these integral representations turn into algebraicones. The asymptotic procedure is justified with the help ofa weighted inequality of Korn's type. The error estimates obtainedgive a rigorous mathematical proof of both of Kirchhoff's hypotheses(kinematic and static) and shed light on the well-known intrinsicinconsistency of two of the hypotheses.     

Some structural peculiarities of CH3COOH-H2O binary mixtures according to proton spin-spin relaxation data

The proton spin-spin relaxation method was used to study the acetic acid-water binary system. The structure of the binary mixture is stabilized over the whole range of concentrations of acetic acid. For heterosolvates, the simplest composition has been determined.Original Russian Text Copyright © 2004 by V. Yu. Buzko, I. V. Sukhno, V. T. Panyushkin, and T. E. DzhioevTranslated from Zhurnal Strukturnoi Khimii, Vol. 45, No. 4, pp. 751–754, July–August, 2004.This revised version was published online in April 2005 with a corrected cover date.     

Some Structural Features of HCOOH-H2O Mixtures According to Proton Spin-Spin Relaxation Data

The structure of the formic acid-water system was studied by proton spin-spin relaxation at 298 K. The simplest compositions of the heterosolvates were determined.