Wyniki wyszukiwania - Biblioteka Nauki

1

Prediction of binding affinities for DNA intercalators by molecular dynamics simulations

100%

Mazerski J.

TASK Quarterly : scientific bulletin of Academic Computer Centre in Gdansk

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2001

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tom Vol. 5, No 3

301-310

EN

The computer modelling and simulation methods are widely used in rational drug design to obtain information necessary for understanding interactions between a ligand (drug molecule) and its cellular macromolecular target on molecular level. The determination of free energies of binding for ligand-target complexes is one of the crucial points in those studies. In recent years several methods have been proposed to solve this problem. The majority of them use molecular dynamics (MD) simulations. Two, most popular methods: (i) a free energy perturbation method (FEP), and (ii) a linear response (LR) method, are shortly presented in this paper together with their limitations and advantages. In this work I presented the first attempt to use LR approach to 10 anti-tumour agents able to intercalate into DNA. The LR relationship obtained in the present study indicated that in the system studied the electrostatic term has no influence on the free energy of binding. The relationship is now successfully used in our research group in further molecular modelling studies concerning DNA intercalators with similar structure.

2

Chemometria w analityce chemicznej. Cz. III. Analiza rozpoznawcza

100%

Mazerski J.

Analityka : nauka i praktyka

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2006

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tom nr 1

4-12

3

Chemometria w analityce chemicznej. Cz. II. Kalibracja wielowymiarowa

100%

Mazerski J.

Analityka : nauka i praktyka

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2005

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tom nr 4

4-10

4

Molecular modelling in the rational design of some anti-tumor and antifungal agents

63%

Mazerski J. , Borowski E.

TASK Quarterly : scientific bulletin of Academic Computer Centre in Gdansk

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1998

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tom Vol. 2, No 4

511-550

EN

In this paper we present our approaches and results concerning application of molecular modelling techniques in the design of new chemotherapeutic agents for the control of eukariotic systems, comprising compounds for the treatment of systemic fungal infections and tumor deseases. In the case of anti-tumor agents we focused our attention on molecular properties of natural and synthetic anthraquinones. In the area of antifungal compounds we adopted two approaches. In one of them we examine molecular nature of undesirable properties of polyene macrolide antifungal antibiotic - amphotericin B using molecular modelling techniques. Another approach was aimed at the development of selective inactivator of glucosamine synthase, a novel target for antifungal compounds. In this problem we have used computational chemistry methods to identify structural features responsible for the selective inactivation of the target enzyme.

5

The intercalation of imidazoacridinones into DNA induces conformational changes in their side chain

63%

Mazerski J. , Muchewicz K.

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2000

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tom 47

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nr 1

EN

Imidazoacridinones (IAs) are a new group of highly active antitumor compounds. The intercalation of the IA molecule into DNA is the preliminary step in the mode of action of these compounds. There are no experimental data about the structure of an intercalation complex formed by imidazoacridinones. Therefore the design of new potentially better compounds of this group should employ the molecular modelling techniques. The results of molecular dynamics simulations performed for four IA analogues are presented. Each of the compounds was studied in two systems: i)in water, and ii)in the intercalation complex with dodecamer duplex d(GCGCGCGCGCGC)2. Significant differences in the conformation of the side chain in the two environments were observed for all studied IAs. These changes were induced by electrostatic as well as van der Waals interactions between the intercalator and DNA. Moreover, the results showed that the geometry of the intercalation complex depends on: i)the chemical constitution of the side chain, and ii)the substituent in position8 of the ring system.

6

Application of chemometric methods in environmental research

51%

Astel A. , Mazerski J. , Namieśnik J.

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2004

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tom Vol. 11, nr 6

417--438

EN

A theoretical description and examples of application of selected chemometrical techniques (cluster analysis, factorial methods, correlation and regression analysis, ANOVA, time series analysis, artificial neural networks) have been presented. Special attention was paid to techniques which, in the authors' opinion, are among the most useful and, at the same time, their application is the most common.

PL

W ostatnich dziesięcioleciach zauważa się dynamiczny wzrost zapotrzebowania na informacje dotyczące otaczającej nas rzeczywistości. Popyt na wiedzę dotyczy zagadnień związanych zarówno ze stanem środowiska, kontrolą jakości procesów przemysłowych i produktów, badań archeologicznych, jak i szerokiego spektrum innych dziedzin. W przypadku badań analitycznych zastosowanie nowoczesnych technik pomiarowych połączone ze skróceniem czasu analiz prowadzi do uzyskiwania obszernych zbiorów danych w stosunkowo krótkim czasie. Zastosowanie specjalnych technik obróbki zbiorów wyników pomiarowych sprawia, że możliwe jest "wydobycie" dodatkowych informacji z posiadanych danych. Idealnym narzędziem do tego typu "zabiegów" może być chemometria. Analiza doniesień literaturowych wskazuje, że z roku na rok wzrasta wykorzystanie technik chemometrycznych w różnych dziedzinach nauki. W opracowaniu omówiono teorię najczęściej wykorzystywanych technik analizy danych (korelacji i analizy regresji, analizy czynników, analizy klasterów, analizy szeregów czasowych i analizy wariancji). Szczególny nacisk położono na omówienie nowoczesnych technik analizy danych zaliczanych do grupy technik sztucznej inteligencji. Opis teoretyczny w każdym przypadku wzbogacono o przykłady zastosowań w konkretnych problemach analitycznych.

7

Rola i dobór wstępnej obróbki surowych widm w analizie jakościowej i ilościowej z wykorzystaniem techniki spektroskopii bliskiej podczerwieni (NIR)

51%

Wrosz P. , Dopierała A. , Mazerski J.

Analityka : nauka i praktyka

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2011

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tom nr 3

24-29

PL

Dla większości laboratoriów kluczowe zagadnienie to czas, koszt i wynik analizy. W większości laboratoriów pracownicy stoją przed presją szybkiego uzyskania wyniku na odpowiednim poziomie precyzji, dokładności oraz wiarygodności.

8

Zastosowanie analizy szeregów czasowych do oceny zanieczyszczenia powietrza atmosferycznego w rejonie Trójmiasta

51%

Astel A. , Mazerski J. , Polkowska Ż. , Namieśnik J.

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tom Vol. 9, nr 8

825-839

PL

Na podstawie analizy wyników pomiarów poziomów stężenia: Na3-, SO4-, F-, Cl, NH4+, P043-, Ca2+, K+ i Mg2+ oraz pomiarów pH i przewodności elektrolitycznej próbek wód opadowych na terenie Trójmiasta z zastosowaniem techniki analizy szeregów czasowych wykazano, że cykliczne wahania poziomów depozycji SO42-, F-, NO3-, Ca2+ i F- w próbkach są skorelowane z cyklicznymi zmianami przeważających kierunków wiatrów. Analiza struktury szeregów czasowych nie wykazała występowania zmian o charakterze cyklicznym w rozkładzie poziomów depozycji jonów NH4+, Cl- i K+. Nie stwierdzono występowania funkcji trendu dla żadnego z badanych analitów.

EN

On the basis of NO3-, SO42-, F-, Cl-, NH4+, PO43-, Ca2+, K+ and Mg2+ concentration levels, and also pH and electrolitycal conductivity of Tricity rainwater with the application of time series it was shown that cyclical variation of SO42-, F-, NO3-, Ca2+ and F- deposition levels in samples were correlated with periodical changes of predominant wind directions. The analysis of the structure of time series did not show any cyclical changes in the levels of NH4+, Cl- and K+ deposition distribution. There was no trend function for any of examined analytes observed in this experiment.

9

Glucosamine-6-phosphate synthase, a novel target for antifungal agents. Molecular modelling studies in drug design

51%

Wojciechowski M. , Milewski S. , Mazerski J. , Borowski E.

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nr 3

EN

Fungal infections are a growing problem in contemporary medicine, yet only a few antifungal agents are used in clinical practice. In our laboratory we proposed the enzyme L-glutamine: D-fructose-6-phosphate amidotransferase (EC 2.6.1.16) as a new target for antifungals. The structure of this enzyme consists of two domains, N-terminal and C-terminal ones, catalysing glutamine hydrolysis and sugar-phosphate isomerisation, respectively. In our laboratory a series of potent selective inhibitors of GlcN-6-P synthase have been designed and synthesised. One group of these compounds, including the most studied N3-(4-methoxyfumaroyl)-l-2,3-diaminopropanoic acid (FMDP), behave like glutamine analogs acting as active-site-directed inactivators, blocking the N-terminal, glutamine-binding domain of the enzyme. The second group of GlcN-6-P synthase inhibitors mimic the transition state of the reaction taking place in the C-terminal sugar isomerising domain. Surprisingly, in spite of the fact that glutamine is the source of nitrogen for a number of enzymes it turned out that the glutamine analogue FMDP and its derivatives are selective against GlcN-6-P synthase and they do not block other enzymes, even belonging to the same family of glutamine amidotransferases. Our molecular modelling studies of this phenomenon revealed that even within the family of related enzymes substantial differences may exist in the geometry of the active site. In the case of the glutamine amidotransferase family the glutamine binding site of GlcN-6-P synthase fits a different region of the glutamine conformational space than other amidotransferases. Detailed analysis of the interaction pattern for the best known, so far, inhibitor of the sugar isomerising domain, namely 2-amino-2-deoxy-d-glucitol-6-phosphate (ADGP), allowed us to suggest changes in the structure of the inhibitor that should improve the interaction pattern. The novel ligand was designed and synthesised. Biological experiments confirmed our predictions. The new compound named ADMP is a much better inhibitor of glucosamine-6-phosphate synthase than ADGP.

10

The geometry of intercalation complex of antitumor mitoxantrone and ametantrone with DNA: Molecular dynamics simulations

51%

Mazerski J. , Martelli S. , Borowski E.

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nr 1

EN

Intercalative binding of the antitumor drugs ametantrone and mitoxantrone to the dodecamer duplex d(CGCGAGCTCGCG)2 was studied by applying molecular dynamics in water with the GROMOS 87 force field. A number of reasonable binding orientations were tested by short pre-simulations. It was shown that in energetically favorable orientation the anthraquinone chromophore is perpendicular to the direction of inter-base hydrogen bonds. Helically shaped side-chains of the drugs fit to the minor groove. The best orientation obtained in pre-simulations was applied in the main simulations. Small but significant differences were found between structures of intercalation complexes of the two drugs with the dodecamer duplex, the mitoxantrone complex possessing more favorable energy. The molecular nature of interactions responsible for those differences has been discussed.

11

The role of side chains in the interaction of new antitumor pyrimidoacridinetriones with DNA: molecular dynamics simulations

51%

Mazerski J. , Antonini I. , Martelli S.

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2000

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tom 47

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nr 1

EN

Pyrimidoacridinetriones (PATs) are a new group of highly active antitumor compounds. It seems reasonable to assume that, like for some other acridine derivatives, intercalation into DNA is a necessary, however not a sufficient condition for antitumor activity of these compounds. Rational design of new compounds of this chemotype requires knowledge about the structure of the intercalation complex, as well as about interactions responsible for its stability. Computer simulation techniques such as molecular dynamics (MD) may provide valuable information about these problems. The results of MD simulations performed for three rationally selected PATs are presented in this paper. The compounds differ in the number and position of side chains. Each of the compounds was simulated in two systems: i)in water, and ii) in the intercalation complex with the dodecamer duplex d(GCGCGCGCGCGC)2. The orientation of the side chain in relation to the ring system is determined by the position of its attachment. Orientation of the ring system inside the intercalation cavity depends on the number and position of side chain(s). The conformations of the side chain(s) of all PATs studied in the intercalation complex were found to be very similar to those observed in water.