Piotr Stępniak

How-to on building a contaminating tissue definition in Microarray Inspector. Analysis of smooth muscle contamination in public microarray data.

We present a bioinformatic tool for performing a posteriori investigation of microarray result files for possible admixtures of unintended tissues.

The study intended to investigate the influence of the two active site residues 216
and 483 on the capability of CYP2D6 to hydroxylate steroids such as testosterone.

Baeyer-Villiger monooxygenases catalyze oxidations that are of interest for biocatalytic applications. Among these enzymes, phenylacetone monooxygenase (PAMO) from Thermobifida fusca is the only protein showing remarkable stability. While related enzymes often present a broad substrate scope, PAMO accepts only a limited number of substrates. Due to the absence of a substrate in the elucidated crystal structure of PAMO, the substrate binding site of this protein has not yet been defined. In this… Pokaż więcej

Baeyer-Villiger monooxygenases catalyze oxidations that are of interest for biocatalytic applications. Among these enzymes, phenylacetone monooxygenase (PAMO) from Thermobifida fusca is the only protein showing remarkable stability. While related enzymes often present a broad substrate scope, PAMO accepts only a limited number of substrates. Due to the absence of a substrate in the elucidated crystal structure of PAMO, the substrate binding site of this protein has not yet been defined. In this study, a structural model of cyclopentanone monooxygenase, which acts on a broad range of compounds, has been prepared and compared with the structure of PAMO. This revealed fifteen amino acid positions in the active site of PAMO that may account for its relatively narrow substrate specificity. We designed and analyzed thirty single and multiple mutants... Pokaż mniej

Squalene epoxidase (SE) is a key flavin adenine dinucleotide (FAD)-dependent enzyme of ergosterol and cholesterol biosynthetic pathways and an attractive potential target for drugs used to inhibit the growth of pathogenic fungi or to lower cholesterol level. Although many studies on allylamine drugs activity have been published during the last 30 years, up until now no detailed mechanism of the squalene epoxidase inhibition has been presented. (...) Docking studies followed by molecular… Pokaż więcej

Squalene epoxidase (SE) is a key flavin adenine dinucleotide (FAD)-dependent enzyme of ergosterol and cholesterol biosynthetic pathways and an attractive potential target for drugs used to inhibit the growth of pathogenic fungi or to lower cholesterol level. Although many studies on allylamine drugs activity have been published during the last 30 years, up until now no detailed mechanism of the squalene epoxidase inhibition has been presented. (...) Docking studies followed by molecular dynamics simulations and quantum interaction energy calculations [MP2/6-31G(d)] resulted in the identification of the terbinafine−squalene epoxidase mode of interaction. In the energetically most likely orientation of terbinafine its interaction energy with the protein is ca. 120 kJ/mol. In the favorable position the terbinafine lipophilic moiety is located vertically inside the squalene epoxidase binding pocket with the tert-butyl group oriented toward its center. Such a position results in the SE conformational changes and prevents the natural substrate from being able to bind to the enzyme’s active site. That would explain the noncompetitive manner of SE inhibition.(...) Our results, elucidating at a molecular level the mode of terbinafine inhibitory activity, can be utilized in designing more potent or selective antifungal drugs or even medicines lowering cholesterol in humans. Pokaż mniej

Here, the general aspects of Virtual Laboratory systems are presented, together with perspectives of their implementation in genomics in order to automate and facilitate this area of research.

Specialized software, on-line tools and computational resources are very common in contemporary science. One of the exemplary domain is genomics – a new branch of science that developed rapidly in the last decade. As the genome research is very complex, it must be supported by professional informatics. In a microarray field the following steps cannot be performed without computational work: design of probes, quantitative analysis of hybridization results, post-processing, and finally data… Pokaż więcej

Specialized software, on-line tools and computational resources are very common in contemporary science. One of the exemplary domain is genomics – a new branch of science that developed rapidly in the last decade. As the genome research is very complex, it must be supported by professional informatics. In a microarray field the following steps cannot be performed without computational work: design of probes, quantitative analysis of hybridization results, post-processing, and finally data storage and management. Here, the general aspects of virtual laboratory systems are presented together with perspectives of their implementation in genomics in order to automate and facilitate this area of research. Pokaż mniej

The paper gives an overview of common methods applied in microarray data analysis. High density oligonucleotide and low density home made microarray types are being considered. Presented exploration procedures follow preprocessing and higher analysis steps, including example methods. Describing higher analysis algorithms we focus on implementation of pattern search and machine learning approaches.