Vsevolod Tanchuk - Academia.edu (original) (raw)
Papers by Vsevolod Tanchuk
Introduction HPLC method development for the analysis of mixtures of substances is a task that us... more Introduction HPLC method development for the analysis of mixtures of substances is a task that usually requires much expertise. It is also extremely time-consuming. In spite of advances in chromatographic theory, HPLC method development is still based mainly on “trial and error”. Consequently, many attempts have been made to use computer programs to facilitate this process. In general, these are stand-alone programs, such as ChromSword (Merck KGaA, Darmstadt, Germany) (1, 2), DryLab (LC Resources, Walnut Creek, California, USA) (3, 4) and others, which have been reviewed in detail (3, 4). Much less commercially available, system-integrated software has been described, in spite of substantial efforts to automate HPLC method development and to design reliable automated systems capable of optimizing separations in a reasonable time. ISOS (Agilent Technologies, Wilmington, Delaware, USA), DIAMOND (ATI, Cambridge, UK) and PESOS (Perkin-Elmer Corp., Norwalk, Connecticut, USA) are examples...
American Laboratory, 2001
Spectra analyse, 2002
Le developpement de methodes de separation est l'objectif le plus important, mais aussi le pl... more Le developpement de methodes de separation est l'objectif le plus important, mais aussi le plus difficile a atteindre en Chromatographie Liquide haute Performance (CLHP). L'utilisation de programmes informatiques specialises peut aider l'analyste a mener a bien cette tâche. De tels programmes permettent en effet, de piloter « intelligemment » une chaine de CLHP dans le cadre du developpement de methodes separatives, et ce en mode automatique. Les paragraphes qui suivent sont consacres a l'utilisation du logiciel Chromsword® pour la mise au point et le developpement de methodes en CLHP. Ce logiciel est capable de fonctionner automatiquement, comme un assistant virtuel, pour gerer en mode continu le procede de developpement de methodes. Il peut egalement fonctionner en mode discontinu comme un expert impartial dans le cadre de l'optimisation de methodes en CLHP.
Computational Biology and Chemistry, 2016
Microtubules play a significant role in cell growth and functioning. Therefore inhibition of the ... more Microtubules play a significant role in cell growth and functioning. Therefore inhibition of the microtubule assemblies has emerged as one of the most promising cancer treatment strategies. Predictive QSAR models were built on a series of selective inhibitors of the tubulin were performed by using Associative Neural Networks (ANN). To overcome the problem of data overfitting due to the descriptor selection, a 5-fold cross-validation with variable selection in each step of the analysis was used. All developed QSAR models showed excellent statistics on the training (total accuracy: 0.96-0.97) and test sets (total accuracy: 0.95-97). The models were further validated by 11 synthesized 1,3-oxazole derivatives and all of them showed inhibitory effect on the Hep-2 cancer cell line. The most promising compound showed inhibitory activity IC 50 = 60.2 mM. In order to hypothesize their mechanism of action the top three compounds were docked in the colchicine binding site of tubulin and showed reasonable docking scores as well as favorable interactions with the protein.
AIP Conference Proceedings, 1995
Artificial neural networks were used to analyze and predict the human immunodefiency virus type 1... more Artificial neural networks were used to analyze and predict the human immunodefiency virus type 1 reverse transcriptase inhibitors. Training and control set included 44 molecules (most of them are well-known substances such as AZT, TIBO, dde, etc.) The biological activities of molecules were taken from literature and rated for two classes: active and inactive compounds according to their values. We
Proceedings of the National Aviation University, 2014
За допомогою докінгу відомих інгібіторів досліджено типові конформації протеїнтирозинфосфатази 1B... more За допомогою докінгу відомих інгібіторів досліджено типові конформації протеїнтирозинфосфатази 1B.Найкращої конформації не виявлено, хоча для кожного інгібітора існує найбільш відповідна конформація.
Chemical Biology Letters, Feb 5, 2015
In vitro assays 1 Docking studies 1 Synthesis of calix[4]arene derivatives 2 References 3
AIP Conference Proceedings, 1995
Current Drug Discovery Technologies, 2015
Molecular docking of small molecules in the protein binding sites is the most widely used computa... more Molecular docking of small molecules in the protein binding sites is the most widely used computational technique in modern structure-based drug discovery. Although accurate prediction of binding modes of small molecules can be achieved in most cases, estimation of their binding affinities remains mediocre at best. As an attempt to improve the correlation between the inhibitory constants, pKi, and scoring, we created a new, hybrid scoring function. The new function is a linear combination of the terms of the scoring functions of AutoDock and AutoDock Vina. It was trained on 2,412 protein-ligand complexes from the PDBbind database (www.pdbbind.org.cn, version 2012) and validated on a set of 313 complexes released in the 2013 version as a test set. The new function was included in a modified version of AutoDock. The hybrid scoring function showed a statistically significant improvement in both training and test sets in terms of correlation with and root mean square and mean absolute errors in prediction of pKi values. It was also tested on the CSAR 2014 Benchmark Exercise dataset (team T) and produced reasonably good results.
Mendeleev Communications, 2015
Proceedings of IEEE Symposium on Computer-Based Medical Systems (CBMS)
Arrificial neural networks were used to analyze the human immunodefiency virus type 1 reverse tra... more Arrificial neural networks were used to analyze the human immunodefiency virus type 1 reverse transcriptase inhibitors and to evaluate newly sinthesized substances on this basis. Training and control set included 44 molecules (most of them are well-known substances such as AZT, &e, etc.). The activities of molecules were taken from literature. Topological indices were calculated and used as molecular parameters. Four most informative parameters were chosen and applied to predict activities of both new and control molecules. We used a network pruning algorithm and network ensembles to obtain the final classifier. The increasing of neural network generalization of the new data was observed, when using the aforementioned methodr. The prognosis of new molecules revealed one molecule as possibly very active. The activity was confirmed by further biological tests.
Current Computer Aided-Drug Design, 2015
Quantitative structure-activity relationship studies on a series of selective inhibitors of throm... more Quantitative structure-activity relationship studies on a series of selective inhibitors of thrombin and factor Xa were performed by using Associative Neural Network. To overcome the problem of overfitting due to descriptor selection, 5-fold cross-validation with variable selection in each step of the analysis was performed. The predictive ability of the models was tested through leave-one-out cross-validation, giving a Q(2)=0.74 - 0.87 for regression models. Predictions for the external evaluation sets obtained accuracies in the range of 0.71 - 0.82 for regressions. The proposed models can be potential tools for finding new drug candidates.
Org. Biomol. Chem., 2015
α,α-Difluoro-β-ketophosphonate derivatives of tetraazamacrocycles were synthesized and found to b... more α,α-Difluoro-β-ketophosphonate derivatives of tetraazamacrocycles were synthesized and found to be potential inhibitors of protein tyrosine phosphatases.
Russian Journal of Bioorganic Chemistry, 2008
A series of thioureido derivatives of methylenebisphosphonic acid were synthesized by the reactio... more A series of thioureido derivatives of methylenebisphosphonic acid were synthesized by the reaction of aminomethylenebisphosphonic acid with the corresponding isothiocyanates, and their effect on the activity of alkaline phosphatases from bovine small intestine mucosa (BSIM) and human placenta was studied. It was found that (3-phenylthioureido)methylenebisphosphonate is approximately one order of magnitude more effective in inhibiting the activity of alkaline phosphatase
Journal of Molecular Graphics and Modelling, 2012
A series of diverse organic compounds, phosphodiesterase type 4 (PDE-4) inhibitors, have been mod... more A series of diverse organic compounds, phosphodiesterase type 4 (PDE-4) inhibitors, have been modeled using a QSAR-based approach. 48 QSAR models were compared by following the same procedure with different combinations of descriptors and machine learning methods. QSAR methodologies used random forests and associative neural networks. The predictive ability of the models was tested through leaveone-out cross-validation, giving a Q 2 = 0.66-0.78 for regression models and total accuracies Ac = 0.85-0.91 for classification models. Predictions for the external evaluation sets obtained accuracies in the range of 0.82-0.88 (for active/inactive classifications) and Q 2 = 0.62-0.76 for regressions. The method showed itself to be a potential tool for estimation of IC 50 of new drug-like candidates at early stages of drug development.
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2009
ABSTRACT AbstractEffect of thiacalix[4]arene platform on inhibition of alkaline phosphatase by ma... more ABSTRACT AbstractEffect of thiacalix[4]arene platform on inhibition of alkaline phosphatase by macrocyclic phosphonate is presented in this article. Using tetrakis(dihydroxyphosphorylmethyl) derivatives we have found that phosphonate inhibitor on thiacalix[4]arene platform has displayed stronger inhibition properties towards alkaline phosphatases from bovine intestine mucosa, shrimp and human placenta than its structural calix[4]arene analogue. For elucidation of the molecular mechanism of the inhibition the tested macrocyclic compounds were docked computationally to the active site of alkaline phosphatase from shrimp. The role of thiacalix[4]arene platform in formation of the enzyme-inhibitor complex is discussed. Graphical AbstractThiacalix[4]arene as molecular platform for design of alkaline phosphatase inhibitors KeywordsCalix[4]arene-Thiacalix[4]arene-Phosphonic acid-Alkaline phosphatase-Inhibition-Molecular docking
Journal of Computer-Aided Molecular Design, 2005
Internet technology offers an excellent opportunity for the development of tools by the cooperati... more Internet technology offers an excellent opportunity for the development of tools by the cooperative effort of various groups and institutions. We have developed a multi-platform software system, Virtual Computational Chemistry Laboratory, http://www.vcclab.org, allowing the computational chemist to perform a comprehensive series of molecular indices/properties calculations and data analysis. The implemented software is based on a three-tier architecture that is one of the standard technologies to provide client-server services on the Internet. The developed software includes several popular programs, including the indices generation program, DRAGON, a 3D structure generator, CORINA, a program to predict lipophilicity and aqueous solubility of chemicals, ALOGPS and others. All these programs are running at the host institutes located in five countries over Europe. In this article we review the main features and statistics of the developed system that can be used as a prototype for academic and industry models.
Introduction HPLC method development for the analysis of mixtures of substances is a task that us... more Introduction HPLC method development for the analysis of mixtures of substances is a task that usually requires much expertise. It is also extremely time-consuming. In spite of advances in chromatographic theory, HPLC method development is still based mainly on “trial and error”. Consequently, many attempts have been made to use computer programs to facilitate this process. In general, these are stand-alone programs, such as ChromSword (Merck KGaA, Darmstadt, Germany) (1, 2), DryLab (LC Resources, Walnut Creek, California, USA) (3, 4) and others, which have been reviewed in detail (3, 4). Much less commercially available, system-integrated software has been described, in spite of substantial efforts to automate HPLC method development and to design reliable automated systems capable of optimizing separations in a reasonable time. ISOS (Agilent Technologies, Wilmington, Delaware, USA), DIAMOND (ATI, Cambridge, UK) and PESOS (Perkin-Elmer Corp., Norwalk, Connecticut, USA) are examples...
American Laboratory, 2001
Spectra analyse, 2002
Le developpement de methodes de separation est l'objectif le plus important, mais aussi le pl... more Le developpement de methodes de separation est l'objectif le plus important, mais aussi le plus difficile a atteindre en Chromatographie Liquide haute Performance (CLHP). L'utilisation de programmes informatiques specialises peut aider l'analyste a mener a bien cette tâche. De tels programmes permettent en effet, de piloter « intelligemment » une chaine de CLHP dans le cadre du developpement de methodes separatives, et ce en mode automatique. Les paragraphes qui suivent sont consacres a l'utilisation du logiciel Chromsword® pour la mise au point et le developpement de methodes en CLHP. Ce logiciel est capable de fonctionner automatiquement, comme un assistant virtuel, pour gerer en mode continu le procede de developpement de methodes. Il peut egalement fonctionner en mode discontinu comme un expert impartial dans le cadre de l'optimisation de methodes en CLHP.
Computational Biology and Chemistry, 2016
Microtubules play a significant role in cell growth and functioning. Therefore inhibition of the ... more Microtubules play a significant role in cell growth and functioning. Therefore inhibition of the microtubule assemblies has emerged as one of the most promising cancer treatment strategies. Predictive QSAR models were built on a series of selective inhibitors of the tubulin were performed by using Associative Neural Networks (ANN). To overcome the problem of data overfitting due to the descriptor selection, a 5-fold cross-validation with variable selection in each step of the analysis was used. All developed QSAR models showed excellent statistics on the training (total accuracy: 0.96-0.97) and test sets (total accuracy: 0.95-97). The models were further validated by 11 synthesized 1,3-oxazole derivatives and all of them showed inhibitory effect on the Hep-2 cancer cell line. The most promising compound showed inhibitory activity IC 50 = 60.2 mM. In order to hypothesize their mechanism of action the top three compounds were docked in the colchicine binding site of tubulin and showed reasonable docking scores as well as favorable interactions with the protein.
AIP Conference Proceedings, 1995
Artificial neural networks were used to analyze and predict the human immunodefiency virus type 1... more Artificial neural networks were used to analyze and predict the human immunodefiency virus type 1 reverse transcriptase inhibitors. Training and control set included 44 molecules (most of them are well-known substances such as AZT, TIBO, dde, etc.) The biological activities of molecules were taken from literature and rated for two classes: active and inactive compounds according to their values. We
Proceedings of the National Aviation University, 2014
За допомогою докінгу відомих інгібіторів досліджено типові конформації протеїнтирозинфосфатази 1B... more За допомогою докінгу відомих інгібіторів досліджено типові конформації протеїнтирозинфосфатази 1B.Найкращої конформації не виявлено, хоча для кожного інгібітора існує найбільш відповідна конформація.
Chemical Biology Letters, Feb 5, 2015
In vitro assays 1 Docking studies 1 Synthesis of calix[4]arene derivatives 2 References 3
AIP Conference Proceedings, 1995
Current Drug Discovery Technologies, 2015
Molecular docking of small molecules in the protein binding sites is the most widely used computa... more Molecular docking of small molecules in the protein binding sites is the most widely used computational technique in modern structure-based drug discovery. Although accurate prediction of binding modes of small molecules can be achieved in most cases, estimation of their binding affinities remains mediocre at best. As an attempt to improve the correlation between the inhibitory constants, pKi, and scoring, we created a new, hybrid scoring function. The new function is a linear combination of the terms of the scoring functions of AutoDock and AutoDock Vina. It was trained on 2,412 protein-ligand complexes from the PDBbind database (www.pdbbind.org.cn, version 2012) and validated on a set of 313 complexes released in the 2013 version as a test set. The new function was included in a modified version of AutoDock. The hybrid scoring function showed a statistically significant improvement in both training and test sets in terms of correlation with and root mean square and mean absolute errors in prediction of pKi values. It was also tested on the CSAR 2014 Benchmark Exercise dataset (team T) and produced reasonably good results.
Mendeleev Communications, 2015
Proceedings of IEEE Symposium on Computer-Based Medical Systems (CBMS)
Arrificial neural networks were used to analyze the human immunodefiency virus type 1 reverse tra... more Arrificial neural networks were used to analyze the human immunodefiency virus type 1 reverse transcriptase inhibitors and to evaluate newly sinthesized substances on this basis. Training and control set included 44 molecules (most of them are well-known substances such as AZT, &e, etc.). The activities of molecules were taken from literature. Topological indices were calculated and used as molecular parameters. Four most informative parameters were chosen and applied to predict activities of both new and control molecules. We used a network pruning algorithm and network ensembles to obtain the final classifier. The increasing of neural network generalization of the new data was observed, when using the aforementioned methodr. The prognosis of new molecules revealed one molecule as possibly very active. The activity was confirmed by further biological tests.
Current Computer Aided-Drug Design, 2015
Quantitative structure-activity relationship studies on a series of selective inhibitors of throm... more Quantitative structure-activity relationship studies on a series of selective inhibitors of thrombin and factor Xa were performed by using Associative Neural Network. To overcome the problem of overfitting due to descriptor selection, 5-fold cross-validation with variable selection in each step of the analysis was performed. The predictive ability of the models was tested through leave-one-out cross-validation, giving a Q(2)=0.74 - 0.87 for regression models. Predictions for the external evaluation sets obtained accuracies in the range of 0.71 - 0.82 for regressions. The proposed models can be potential tools for finding new drug candidates.
Org. Biomol. Chem., 2015
α,α-Difluoro-β-ketophosphonate derivatives of tetraazamacrocycles were synthesized and found to b... more α,α-Difluoro-β-ketophosphonate derivatives of tetraazamacrocycles were synthesized and found to be potential inhibitors of protein tyrosine phosphatases.
Russian Journal of Bioorganic Chemistry, 2008
A series of thioureido derivatives of methylenebisphosphonic acid were synthesized by the reactio... more A series of thioureido derivatives of methylenebisphosphonic acid were synthesized by the reaction of aminomethylenebisphosphonic acid with the corresponding isothiocyanates, and their effect on the activity of alkaline phosphatases from bovine small intestine mucosa (BSIM) and human placenta was studied. It was found that (3-phenylthioureido)methylenebisphosphonate is approximately one order of magnitude more effective in inhibiting the activity of alkaline phosphatase
Journal of Molecular Graphics and Modelling, 2012
A series of diverse organic compounds, phosphodiesterase type 4 (PDE-4) inhibitors, have been mod... more A series of diverse organic compounds, phosphodiesterase type 4 (PDE-4) inhibitors, have been modeled using a QSAR-based approach. 48 QSAR models were compared by following the same procedure with different combinations of descriptors and machine learning methods. QSAR methodologies used random forests and associative neural networks. The predictive ability of the models was tested through leaveone-out cross-validation, giving a Q 2 = 0.66-0.78 for regression models and total accuracies Ac = 0.85-0.91 for classification models. Predictions for the external evaluation sets obtained accuracies in the range of 0.82-0.88 (for active/inactive classifications) and Q 2 = 0.62-0.76 for regressions. The method showed itself to be a potential tool for estimation of IC 50 of new drug-like candidates at early stages of drug development.
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2009
ABSTRACT AbstractEffect of thiacalix[4]arene platform on inhibition of alkaline phosphatase by ma... more ABSTRACT AbstractEffect of thiacalix[4]arene platform on inhibition of alkaline phosphatase by macrocyclic phosphonate is presented in this article. Using tetrakis(dihydroxyphosphorylmethyl) derivatives we have found that phosphonate inhibitor on thiacalix[4]arene platform has displayed stronger inhibition properties towards alkaline phosphatases from bovine intestine mucosa, shrimp and human placenta than its structural calix[4]arene analogue. For elucidation of the molecular mechanism of the inhibition the tested macrocyclic compounds were docked computationally to the active site of alkaline phosphatase from shrimp. The role of thiacalix[4]arene platform in formation of the enzyme-inhibitor complex is discussed. Graphical AbstractThiacalix[4]arene as molecular platform for design of alkaline phosphatase inhibitors KeywordsCalix[4]arene-Thiacalix[4]arene-Phosphonic acid-Alkaline phosphatase-Inhibition-Molecular docking
Journal of Computer-Aided Molecular Design, 2005
Internet technology offers an excellent opportunity for the development of tools by the cooperati... more Internet technology offers an excellent opportunity for the development of tools by the cooperative effort of various groups and institutions. We have developed a multi-platform software system, Virtual Computational Chemistry Laboratory, http://www.vcclab.org, allowing the computational chemist to perform a comprehensive series of molecular indices/properties calculations and data analysis. The implemented software is based on a three-tier architecture that is one of the standard technologies to provide client-server services on the Internet. The developed software includes several popular programs, including the indices generation program, DRAGON, a 3D structure generator, CORINA, a program to predict lipophilicity and aqueous solubility of chemicals, ALOGPS and others. All these programs are running at the host institutes located in five countries over Europe. In this article we review the main features and statistics of the developed system that can be used as a prototype for academic and industry models.