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1

Fragment Aβ(18-41) presented within the CDR3 loop region of a shark immunoglobulin new antigen receptor single-variable domain antibody analyzed based on the fuzzy oil drop model

Banach M., Konieczny L., Wiśniowski Z., Roterman I.

Bio-Algorithms and Med-Systems

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2018

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Vol. 14, no. 3

art. no. 20180028

EN

The structure of amyloid Aβ(1-41) is the object of many papers due to the neurodegenerative processes induced by this amyloid. One of the ways to investigate the possible structural forms other than the amyloid is to incorporate the fragment of this peptide into the chain of immunoglobulin. Fragment Aβ(18-41) presented within the CDR3 loop region of a shark immunoglobulin new antigen receptor single-variable domain antibody is the object of this analysis. The structure of this hybrid is available in the PDB and analyzed based on the fuzzy oil drop model. The aim is to define the status of this fragment, revealing the possible fitting to the ordered form of the hydrophobic core. Simultaneously, the verification of the predisposition to complexation is possible.

2

Comparison of the structure of Aβ(1-40) amyloid with the one in complex with polyphenol ε-viniferin glucoside (EVG)

Dułak D., Banach M., Wiśniowski Z., Konieczny L., Roterman I.

Bio-Algorithms and Med-Systems

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2018

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Vol. 14, no. 2

art. no. 20180008

EN

The analysis of amyloid structures is much easier recently due to the availability of the solid-state nuclear magnetic resonance technique, which allows the determination of the 3D structure of amyloid forms. The amyloidogenic polypeptide Aβ(1-40) (PDB ID 2M9R, 2M9S) in its soluble form is the object of analysis in this paper. The solubility of this polypeptide is reached due to the presence of a complexed ligand: polyphenol ε-viniferin glucoside. Two forms of complexes available in the PDB were taken for analysis with respect to the presence of a hydrophobic core in the 3D structure of these complexes. The idealized hydrophobic core structure assumed to be accordant with the 3D Gauss function distribution was taken as the pattern. The aim of this analysis is the possible further comparison to the structures of the hydrophobic core present in amyloids. It is shown that the discordant (versus the 3D Gauss function) fragments present in amyloids appear accordant in the discussed complexes.

3

Chromatin 3D - will it make understanding of cancer transformation finally possible?

Drabik G., Kaszuba-Zwoińska J., Wiśniowski Z., Konieczny L., Roterman I.

Bio-Algorithms and Med-Systems

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2018

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Vol. 14, no. 1

art. no. 20180002

EN

Despite enormous progress in molecular analysis of cancer cell genomes, the mechanism of tumorigenesis remains unclear. The information present in the genome is not limited to the DNA sequence itself. Indeed, a significant portion of this information is concealed in the spatial structure of chromatin. Ongoing scientific studies that focus on the three-dimensional structure of chromatin raise hopes of arriving at a general explanation of the cancer transformation phenomenon.

4

The variability of protein structure with respect to the hydrophobic core

Banach M., Wiśniowski Z., Kalinowska B., Konieczny L., Roterman I.

Bio-Algorithms and Med-Systems

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2017

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Vol. 13, no. 2

63--67

EN

The application of the fuzzy oil drop model to the analysis of protein structure is shown using two proteins. The selection of these two examples is due to their opposite character. Two proteins were selected representing very high order and very high disorder with respect to the organized uni-central hydrophobic core in proteins (one centrally localized concentration of high hydrophobicity). These two cases are to show examples of the large spectrum of variability of local organization of the hydrophobic core in proteins. The importance of the observation presented in this paper is significant with respect to large sets of proteins discussed in separate publications.

5

Structure of hydrophobic core in plant carboxylesterase

Banach M., Konieczny L., Wiśniowski Z., Roterman I.

Bio-Algorithms and Med-Systems

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2017

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Vol. 13, no. 1

13--16

EN

The fuzzy oil drop model was applied to characterize the hydrophobic core structure in plant carboxylesterase. The characteristics revealed the status of β-sheets in the central part of the molecule as discordant as opposed to the expected hydrophobicity distribution. Particularly, the β-strands and helices in close proximity to the enzymatic residues recognized as discordant with respect to the ideal hydrophobicity distribution of hydrophobic core are of high importance. It is assumed that this local irregularity is the form of coding the specificity of enzymes. The protein under consideration appears to be the next example proving this assumption.

6

Role of the hydrophobic core in cytoskeleton protein: cardiac myosin binding protein C

Gołda M., Banach M., Wiśniowski Z., Ziajka W., Roterman I.

Bio-Algorithms and Med-Systems

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2017

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Vol. 13, no. 3

161--165

EN

Cardiac myosin binding protein C is the object of analysis presented in this paper. The fuzzy oil drop model was applied to analyze the status of the hydrophobic core in two forms of this protein: WT and R502W mutant. The status of the mutant is revealed to be of lower stability than the WT form. The high order of the hydrophobic core is interpreted as the factor of stability of the tertiary structure. The muscle proteins, which undergo significant structural changes as the consequence of external stretching forces, are expected to return to initial structures after the release of an external force. The mutant R502W appears to represent lower stability; thus, the return to the initial structure may be of lower probability. The comparable analysis to other muscle domains (titin) and immunoglobulin domains suggests the very subtle relation to the biological activity of these proteins.

7

Mechanism of ligand binding – PDZ domain taken as example

Dułak D., Banach M., Wiśniowski Z., Konieczny L., Roterman I.

Bio-Algorithms and Med-Systems

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2017

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Vol. 13, no. 4

175--178

EN

Abstract: The mechanism of specific ligand binding by proteins is discussed using the PDZ domain complexing the pentapeptide. This process is critical for clustering the membrane ion channel. The traditional model based on the Beta-sheet extension by complexed pentapeptide is interpreted as a hydrophobic core extension supported by additional Beta-strand generated by complexed pentapeptide. The explanation is based on the fuzzy oil drop model applied to the crystal structure of PDZ-pentapeptide.

8

Chain-chain complexation and heme binding in haemoglobin with respect to the hydrophobic core structure

Ptak M., Banach M., Wiśniowski Z., Konieczny L., Roterman I.

Bio-Algorithms and Med-Systems

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2017

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Vol. 13, no. 4

179--185

EN

Heme binding by proteins and protein-protein complexation are the processes strongly related to the biological activity of proteins. The mechanism of these processes has not been still recognised. These phenomena are presented using haemoglobin as the example. Half of the mature haemoglobin (one α-chain and one β-chain) treated as a dissociation step in haemoglobin degradation reveals a specific change in heme binding after dissociation. This phenomenon is the object of analysis that interprets the structure of both complexes (tetramer and dimer) with respect to their hydrophobic core structure. The results suggest the higher stability of the complex in the form of one α-chain and one β-chain with respect to the hydrophobic core.

9

Structural similarity of CheY-like proteins

Banach M., Konieczny L., Roterman I.

TASK Quarterly : scientific bulletin of Academic Computer Centre in Gdansk

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2016

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Vol. 20, No 4

383--392

EN

The problem of structural similarity of polypeptide chains of low sequence similarity representing a similar 3D structural form has been the object of analysis of researchers engaged in the protein folding problem. Three homologous proteins of similar biological function with low sequence similarity are the objects of analysis presented in this paper. The structure of a hydrophobic core is used as the criterion for structural similarity assessment of these three proteins. The applied method allows recognition of differentiati on in topologically similar structures.

10

Dissimilar sequence: similar structure of proteins

Banach M., Konieczny L., Roterman I.

Bio-Algorithms and Med-Systems

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2016

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Vol. 12, no. 3

117--121

EN

Sequence-to-structure relation is one of the major objects of the analysis of protein folding problem. The pair of two small proteins (domains) of similar structure (β-hairpin/α-helix/β-hairpin) generated by the chains of similar length (about 60 amino acids) with very low sequence similarity (15%) is the object of the comparable analysis of 3D structure. The criterion for similarity estimation is the status of polypeptide chain with respect to the hydrophobic core structure. The fuzzy oil drop model is applied to reveal the differentiated status of fragments of the well-defined secondary structure. This analysis allows the interpretation of the structure in other than the geometric form as it is made based on secondary structure classification. The two compared highly similar proteins appear to be different with respect to the hydrophobic core structure.

11

The use of Titan yellow dye as a metal ion binding marker for studies on the formation of specific complexes by supramolecular Congo red

Chłopaś K., Jagusiak A., Konieczny L., Piekarska B., Roterman I., Rybarska J., Stopa B., Zemanek G., Bielańska E., Piwowar P., Sadlik K.

Bio-Algorithms and Med-Systems

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2015

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Vol. 11, no. 1

9--17

EN

Congo red (CR) and other self-assembling compounds creating supramolecular structures of rod- or ribbon-like architecture form specific complexes with cellulose and also with many proteins, including antibodies bound to the antigen and amyloids in particular. The mechanism of complexation and structure of these complexes are still poorly recognized despite the importance of the problem for medicine. This work proposes the progress in electron microscopy studies of amyloid-dye complexes by labeling supramolecular ligand CR with silver ions as a marker. Silver ions are introduced to CR carried by the strongly binding silver dye Titan yellow, which in addition form comicellar structures with CR. Silver carried by self-assembled dye molecules forms in the resulting metal nanoparticles, making the specific amyloid ligand CR perceptible in EM studies.

12

Speaker identification based on artificial neural networks. Case study: the Polish vowel (pilot study)

Salapa K., Trawińska A., Roterman I., Tadeusiewicz R.

Bio-Algorithms and Med-Systems

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2014

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Vol. 10, no. 2

91--99

EN

Current statistical methods and technologies used for speaker identification via dynamic formant frequency often involve classic multivariate analyses that must meet a number of criteria in order to be considered trustworthy. The authors propose more advanced classification techniques, including artificial neural networks. Owing to iterative learning algorithms, neural networks can be trained to detect highly complex, nonlinear relations hidden in input data. This study specifically considers feed-forward multilayer perceptron and radial basic function network models. The investigation involves an analysis of the Polish vowel (stressed or unstressed) in selected contexts described by the four lowest formant frequencies. Results indicate high accuracy of neural networks as a speaker identification tool reaching up to 100%. In addition, the authors have determined that the accuracy of classification is similar when based on a single context to when input data are aggregated over several different contexts.

13

Attempt at a systemic outlook on aging and carcinogenesis

Piwowar M., Dygut J., Piwowar P., Konieczny L., Roterman I.

Bio-Algorithms and Med-Systems

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2014

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Vol. 10, no. 3

101--115

EN

Two of the key problems plaguing humanity – aging and carcinogenesis – are inexorably linked. While their nature seems different, their mechanisms have a lot in common. Evidence suggests that aging is the result of spontaneous synthesis and accumulation of improperly folded proteins in cells, leading to a variety of pathologies. As for carcinogenesis, it is tied to genetic mutations – permanent, covalent changes in the DNA. Both processes are random in character; however, unlike mutations, the accumulation of malformed proteins is not genetically determined. Instead, control over this process hinges upon regulating the protein exchange rate – a phenomenon that seems a likely candidate for the basic aging control mechanism. Although mutations themselves may be counteracted in a controlled manner, their effects typically cannot. The mechanisms of aging and carcinogenesis, while functionally different, remain correlated: an aging cell is rendered more susceptible to mutational changes. The rapidly growing body of information regarding aging and carcinogenesis enables a systemic approach to both these phenomena – an approach that is attempted in this review.

14

Structural role of exons in hemoglobin

Piwowar M., Banach M., Konieczny L., Chomilier J., Roterman I.

Bio-Algorithms and Med-Systems

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2013

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Vol. 9, no. 2

81--90

EN

The role of exons can be studied on many levels, one of which pertains to protein structure. It is a well-known fact that secondary structural motifs do not directly correspond to exons: helices, β-sheets and loops have all been identified as encoded by more than one exon. The relation between exon fragments and their involvement in shaping the three-dimensional (3D) structure of a protein body is subject to ongoing studies. In particular, the role of exons in stabilizing tertiary structures can be related to the structure of the hydrophobic core of the protein. Participation of specific polypeptide fragments (single exons) in hydrophobic stabilization reveals the role played by each fragment. In the course of the presented research, exons in selected proteins have been identified on the basis of GenBank files, imported from the nucleotide database at the National Center of Biotechnology Information. Amino acid sequences representing each exon were subsequently traced to parts of 3D structural forms. The participation of each exon fragment in shaping the hydrophobic core of the protein was measured using divergence entropy calculations. It was found that each protein contains at least one exon which encodes a structural fragment in accordance with the theoretical hydrophobic core model. This implies that the likely role of at least one exon in each protein is to generate a hydrophobic core which is, in turn, responsible for tertiary structural stabilization.

15

Structural role of exon-coded fragments in proteins

Piwowar M., Banach M., Konieczny L., Roterman I.

Bio-Algorithms and Med-Systems

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2013

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Vol. 9, no. 3

103--114

EN

This article describes the role of protein fragments encoded by individual exons. Structural analysis of the hydrophobic core on the basis of the “fuzzy oil drop” model – in whole molecules as well as in fragments encoded by specific exons – indicates that, in each protein, at least one exon encodes a fragment, which is consistent with the theoretical distribution of hydrophobicity density. Quantitative assessment of the properties of such exons in selected proteins enables the model to be applied in identifying the structural (stabilizing) role of polypeptide chains encoded by individual exons. This is viewed as a preliminary step toward future exploitation of this technique in studying the alternative splicing phenomenon.

16

Technical solutions for bio-measurements

Konieczny L., Markiewicz M., Piwowar P., Roterman I.

Bio-Algorithms and Med-Systems

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2012

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Vol. 8, no. 4

339--349

EN

Biological processes are controlled automatically. Registration of signals and measuring their relative strength is hence a key problem. Receptors may be relatively simple or complex. The complexity is the direct response to ambiguity of signals. If there is however a common feature of diverse signals a construction of generic receptor mechanism is usually observed. Combinatorial technique is commonly used in biological systems to decrease the complexity in reception of highly ambiguous signals.

17

Structural analysis of the lactoferrin iron binding pockets

Marchewka D., Roterman I., Strus M., Śpiewak K., Majka G.

Bio-Algorithms and Med-Systems

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2012

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Vol. 8, no. 4

351--359

EN

Lactoferrin (Lf) - member of the transferrin family of proteins responsible for many different functions in the body of mammals participates in regulation of free iron level in the body fluids making the protein bacteriostatic. The main goal of studies was to test the suitability of molecular dynamic simulation to study structural changes in the tertiary structure of lactoferrin. According to ConSurf Server analysis one of the most conservative amino acids was found not only in iron- but also in carbohydrates- binding pockets which may suggest a significant impact of carbohydrates on the functions performed by lactoferrin. Pocket-Finder program applied to find iron-binding pockets revealed the potential Fe binding area. The stability of the ligand deprived protein was verified performing the 50 ns dynamic simulation using the Gromacs program. The tertiary structure changes during the simulation were observed in N-lob solely. No structural changes were observed in C-lob iron-binding pocket.

18

Stability of two natural homologous proteins with different folds

Konieczny L., Banach M., Roterman I.

Bio-Algorithms and Med-Systems

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2012

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Vol. 8, no. 2

185--193

EN

The applicability of the model for protein folding process simulation is presented using as the test two homologous proteins of different fold: helical in 3BD1 and β-structural form in 2PIJ [L. van Dorn, T. Newlove, S. Chang, W. Ingram, M. Cordes. Biochemistry 45, 10542 (2006)]. The folding process is assumed to be directed by hydrophobic core directing the hydrophobic residues toward the center of the molecule and exposing the hydrophilic residues on the surface. The “fuzzy oil drop” model is expressed by the 3-dimensional Gauss function which mimics the external force field. The value of Gauss function is interpreted as the hydrophobicity density calculated in any point of the space of the protein body. The accordance of idealized and observed hydrophobicity distributions (calculated according to Levitt function) measured using the Kullback-Leibler divergence entropy reveals good accordance in two homological proteins of different folds. The structural differences appeared to be easily explainable on the basis of “fuzzy oil drop” model.

19

Measurement of hydrophobicity distribution in proteins – non-redundant Protein Data Bank

Sałapa K, Kalinowska B., Jadczyk T., Roterman I.

Bio-Algorithms and Med-Systems

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2012

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Vol. 8, no. 3

327--337

EN

The cluster analysis is applied to the analysis of the data describing the status of protein structure in respect to hydrophobic core characteristics. The analysis revealed presence of two clusters distinguishing the proteins accordant with the “fuzzy oil drop” model and those which appear as discordant in respect to this model. The analysis was performed separately for chains treated as structural unit and for units defined according to IV-order (taking the functional protein complex). The characteristics of these two classification system appeared to differ in respect to number of proteins belonging to each of two clusters as well as relation between them.

20

Measurement of hydrophobicity distribution in proteins – complete redundant Protein Data Bank

Sałapa K, Kalinowska B., Jadczyk T., Roterman I.

Bio-Algorithms and Med-Systems

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2012

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Vol. 8, no. 2

195--206

EN

The divergence entropy: O/T and O/R measuring the distance between observed/theoretical and observed/random distributions was applied to identify the category of protein structures in respect to the hydrophobic core in protein molecules. The naive interpretation was applied treating the proteins of O/T < O/R as the molecules of hydrophobic core accordant with the theoretically assumed. The proteins of O/T > O/R are treated as representing the hydrophobic core not accordant with the assumed one. The large scale computing was performed (PDB data set) to reveal whether other than simple inequality relation should be used for this identification. The cluster analysis was applied to identify the relation O/T versus O/R as the discrimination factor to classify the category of proteins in respect to their structural form of hydrophobic core.