Yegor Smurnyy

Publications of Yegor Smurnyy

• Binucleine 2, an isoform-specific inhibitor of Drosophila Aurora B kinase, provides insights into the mechanism of cytokinesis.

  Authors: Yegor Smurnyy, Angela V Toms, Gilles R Hickson, Michael J Eck, Ulrike S Eggert

  ACS chemical biology. 11/2010; 5(11):1015-20.

  Aurora kinases are key regulators of cell division and important targets for cancer therapy. We report that Binucleine 2 is a highly isoform-specific inhibitor of Drosophila Aurora B kinase, and weAurora kinases are key regulators of cell division and important targets for cancer therapy. We report that Binucleine 2 is a highly isoform-specific inhibitor of Drosophila Aurora B kinase, and we identify a single residue within the kinase active site that confers specificity for Aurora B. Using Binucleine 2, we show that Aurora B kinase activity is not required during contractile ring ingression, providing insight into the mechanism of cytokinesis.

• Small molecules discovered in a pathway screen target the Rho pathway in cytokinesis.

  Authors: Adam B Castoreno, Yegor Smurnyy, Angelica D Torres, Martha S Vokes, Thouis R Jones, Anne E Carpenter, Ulrike S Eggert

  Nature chemical biology. 06/2010; 6(6):457-63.

  We report the discovery of small molecules that target the Rho pathway, which is a central regulator of cytokinesis--the final step in cell division. We have developed a way of targeting a smallWe report the discovery of small molecules that target the Rho pathway, which is a central regulator of cytokinesis--the final step in cell division. We have developed a way of targeting a small molecule screen toward a specific pathway, which should be widely applicable to the investigation of any signaling pathway. In a chemical genetic variant of a classical modifier screen, we used RNA interference (RNAi) to sensitize cells and identified small molecules that suppressed or enhanced the RNAi phenotype. We discovered promising candidate molecules, which we named Rhodblock, and we identified the target of Rhodblock as Rho kinase. Several Rhodblocks inhibited one function of the Rho pathway in cells: the correct localization of phosphorylated myosin light chain during cytokinesis. Rhodblocks differentially perturb Rho pathway proteins in cells and can be used to dissect the mechanism of the Rho pathway during cytokinesis.

• Empirical and DFT GIAO quantum-mechanical methods of (13)C chemical shifts prediction: competitors or collaborators?

  Authors: Mikhail Elyashberg, Kirill Blinov, Yegor Smurnyy, Tatiana Churanova, Antony Williams

  Magnetic resonance in chemistry : MRC. 03/2010; 48(3):219-29.

  The accuracy of (13)C chemical shift prediction by both DFT GIAO quantum-mechanical (QM) and empirical methods was compared using 205 structures for which experimental and QM-calculated chemicalThe accuracy of (13)C chemical shift prediction by both DFT GIAO quantum-mechanical (QM) and empirical methods was compared using 205 structures for which experimental and QM-calculated chemical shifts were published in the literature. For these structures, (13)C chemical shifts were calculated using HOSE code and neural network (NN) algorithms developed within our laboratory. In total, 2531 chemical shifts were analyzed and statistically processed. It has been shown that, in general, QM methods are capable of providing similar but inferior accuracy to the empirical approaches, but quite frequently they give larger mean average error values. For the structural set examined in this work, the following mean absolute errors (MAEs) were found: MAE(HOSE) = 1.58 ppm, MAE(NN) = 1.91 ppm and MAE(QM) = 3.29 ppm. A strategy of combined application of both the empirical and DFT GIAO approaches is suggested. The strategy could provide a synergistic effect if the advantages intrinsic to each method are exploited.

• Computer-assisted methods for molecular structure elucidation: realizing a spectroscopist's dream.

  Authors: Mikhail Elyashberg, Kirill Blinov, Sergey Molodtsov, Yegor Smurnyy, Antony J Williams, Tatiana Churanova

  Journal of cheminformatics. 01/2009; 1:3.

  This article coincides with the 40 year anniversary of the first published works devoted to the creation of algorithms for computer-aided structure elucidation (CASE). The general principles on whichThis article coincides with the 40 year anniversary of the first published works devoted to the creation of algorithms for computer-aided structure elucidation (CASE). The general principles on which CASE methods are based will be reviewed and the present state of the art in this field will be described using, as an example, the expert system Structure Elucidator. The developers of CASE systems have been forced to overcome many obstacles hindering the development of a software application capable of drastically reducing the time and effort required to determine the structures of newly isolated organic compounds. Large complex molecules of up to 100 or more skeletal atoms with topological peculiarity can be quickly identified using the expert system Structure Elucidator based on spectral data. Logical analysis of 2D NMR data frequently allows for the detection of the presence of COSY and HMBC correlations of "nonstandard" length. Fuzzy structure generation provides a possibility to obtain the correct solution even in those cases when an unknown number of nonstandard correlations of unknown length are present in the spectra. The relative stereochemistry of big rigid molecules containing many stereocenters can be determined using the StrucEluc system and NOESY/ROESY 2D NMR data for this purpose. The StrucEluc system continues to be developed in order to expand the general applicability, provide improved workflows, usability of the system and increased reliability of the results. It is expected that expert systems similar to that described in this paper will receive increasing acceptance in the next decade and will ultimately be integrated directly to analytical instruments for the purpose of organic analysis. Work in this direction is in progress. In spite of the fact that many difficulties have already been overcome to deliver on the spectroscopist's dream of "fully automated structure elucidation" there is still work to do. Nevertheless, as the efficiency of expert systems is enhanced the solution of increasingly complex structural problems will be achievable.

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• Calculating protein structures directly from anisotropic spin interaction constraints.

  Authors: Yegor Smurnyy, Stanley J Opella

  Magnetic resonance in chemistry : MRC. 04/2006; 44(3):283-93.

  Protein structure determination by solid-state NMR of aligned samples relies on the fundamental characteristics of the anisotropic nuclear spin interactions present in isotopically labeled proteins.Protein structure determination by solid-state NMR of aligned samples relies on the fundamental characteristics of the anisotropic nuclear spin interactions present in isotopically labeled proteins. Progress in the implementation of algorithms that calculate protein structures from the orientational constraints in the chemical shift and heteronuclear dipolar coupling interactions is described using both simulated and experimental data.