A stabilizációs centrumokra vonatkozó információ beépítése fehérje szekvencia-térszerkezet párosító (threading) eljárásba = Incorporation of stabilization centers into threading

A 2003-2006 időszakban végzett kutatómunkám a stabilizációs centrumok azonosítására szolgáló SCIDE nyilvános szerver világhálóra telepítésével kezdődött. A program közepétől tevékenységem kiterjedt a globuláris vízoldható fehérjéken túlra is. Egyrészt kidolgoztuk a TMDET nevű algoritmust, amely alkalmas a transzmembrán fehérjék automatizált megkülönböztetésére és ennek segítségével létrehoztuk a hetente folyamatosan frissülő PDB_TM adatbázist. Emellett elkezdtem foglalkozni az időben állandó térszerkezettel nem rendelkező, úgynevezett rendezetlen fehérjékkel. Ezen a területen a legfontosabb eredményem, hogy kidolgoztam egy eredeti módszert rendezetlen fehérjék illetve fehérje szegmenseknek szekvenciából történő becslésére. | I started the research period of 2003-2006 with setting up the freely accessible web server SCIDE for the identification of stabilization centers. Form the middle of the program my research interest gradually shifted beyond water soluble globular proteins. First, we developed the TMDET algorithm suitable for the automated discrimination of globular and transmembrane proteins, and this allowed establishing the PDB_TM database which is updated on a weekly basis. Furthermore, I become interested in the so-called disordered proteins which do not have a stable well defined three-dimensional structure. My main result on this area was the development of an original method for the prediction of disorder protein and protein segments from the amino acid sequence

A Multipartite Hajnal-Szemer\'edi Theorem

The celebrated Hajnal-Szemer\'edi theorem gives the precise minimum degree threshold that forces a graph to contain a perfect K_k-packing. Fischer's conjecture states that the analogous result holds for all multipartite graphs except for those formed by a single construction. Recently, we deduced an approximate version of this conjecture from new results on perfect matchings in hypergraphs. In this paper, we apply a stability analysis to the extremal cases of this argument, thus showing that the exact conjecture holds for any sufficiently large graph.Comment: Final version, accepted to appear in JCTB. 43 pages, 2 figure

Economic spatial modeling of Eger and Miskolc on maps with different GIS methods

In this study we did the economic spatial modeling of the cities of Eger and Miskolc on maps with different GIS methods. The aim was to produce maps that accurately display the nodes and the operating time interval of companies in different national economic sectors within a given city. The geo-referencing of the available settlement planning maps was necessary for the city of Miskolc. Both GIS and enterprise database building are required to produce the aforementioned results, for which we have used various software and methods

Functionally and structurally relevant residues of enzymes: are they segregated or overlapping?

AbstractThere is a delicate balance between stability and flexibility needed for enzyme function. To avoid undesirable alteration of the functional properties during the evolutionary optimization of the structural stability under certain circumstances, and vice versa, to avoid unwanted changes of stability during the optimization of the functional properties of proteins, common sense would suggest that parts of the protein structure responsible for stability and parts responsible for function developed and evolved separately. This study shows that nature did not follow this anthropomorphic logic: the set of residues involved in function and those involved in structural stabilization of enzymes are rather overlapping than segregated

Fájdalomcsillapító-túlhasználathoz társuló fejfájás

Absztrakt A fájdalomcsillapító-túlhasználathoz társuló fejfájás a lakosság 1–2%-át érinti. Bármely fájdalomcsillapító rendszeres, havonta legalább 10 napon történő szedése kiválthatja, ezért minden olyan esetben gondolni kell rá, amikor korábban is panaszos betegek fejfájásának gyakorisága – nagyobb mennyiségben szedett fájdalomcsillapítók mellett – megnő. A kórkép leggyakrabban a 40–50 éves nőket érinti: kockázatát növeli a dohányzás, az elhízás, a depresszió, valamint a szorongásos zavar. Kialakulásában biológiai (genetikai megalapozottság, neurokémiai és neurofiziológiai eltérések) mellett pszichológiai, illetve életvezetési tényezők, így a fejfájásokra vonatkozó anticipátoros szorongás, a fájdalom katasztrofizálása, az ezek miatti kényszeres gyógyszerszedő magatartás is fontos szerepet játszanak. A fájdalomcsillapító-túlhasználathoz társuló fejfájás kezelésének elengedhetetlen része a kiváltó szer megvonása, a megvonási tünetek (köztük a rebound fejfájás) kezelése, a hatásos preventív terápia bevezetése, a komorbid betegségek kezelése, valamint a betegek megfelelő oktatása és pszichés támogatása. Mivel a visszaesés esélye megfelelő kezelés mellett is 30–40% lehet, alapvető fontosságú a megelőzés, amelyben az alapellátás szerepét nem lehet eléggé hangsúlyozni. Orv. Hetil., 2015, 156(30), 1195–1202

Cell cycle control by the target of rapamycin signalling pathway in plants

Cells need to ensure a sufficient nutrient and energy supply before committing to proliferate. In response to positive mitogenic signals, such as light, sugar availability, and hormones, the target of rapamycin (TOR) signalling pathway promotes cell growth that connects to the entry and passage through the cell division cycle via multiple signalling mechanisms. Here, we summarize current understanding of cell cycle regulation by the RBR-E2F regulatory hub and the DREAM-like complexes, and highlight possible functional relationships between these regulators and TOR signalling. A genetic screen recently uncovered a downstream signalling component to TOR that regulates cell proliferation, YAK1, a member of the dual specificity tyrosine phosphorylation-regulated kinase (DYRK) family. YAK1 activates the plant-specific SIAMESE-RELATED (SMR) cyclin-dependent kinase inhibitors and therefore could be important to regulate both the CDKA-RBR-E2F pathway to control the G1/S transition and the mitotic CDKB1;1 to control the G2/M transition. TOR, as a master regulator of both protein synthesis-driven cell growth and cell proliferation is also central for cell size homeostasis. We conclude the review by briefly highlighting the potential applications of combining TOR and cell cycle knowledge in the context of ensuring future food security

The role of stabilization centers in protein thermal stability

AbstractThe definition of stabilization centers was introduced almost two decades ago. They are centers of noncovalent long range interaction clusters, believed to have a role in maintaining the three-dimensional structure of proteins by preventing their decay due to their cooperative long range interactions. Here, this hypothesis is investigated from the viewpoint of thermal stability for the first time, using a large protein thermodynamics database. The positions of amino acids belonging to stabilization centers are correlated with available experimental thermodynamic data on protein thermal stability. Our analysis suggests that stabilization centers, especially solvent exposed ones, do contribute to the thermal stabilization of proteins

Access Path to the Ligand Binding Pocket May Play a Role in Xenobiotics Selection by AhR.

Understanding of multidrug binding at the atomic level would facilitate drug design and strategies to modulate drug metabolism, including drug transport, oxidation, and conjugation. Therefore we explored the mechanism of promiscuous binding of small molecules by studying the ligand binding domain, the PAS-B domain of the aryl hydrocarbon receptor (AhR). Because of the low sequence identities of PAS domains to be used for homology modeling, structural features of the widely employed HIF-2alpha and a more recent suitable template, CLOCK were compared. These structures were used to build AhR PAS-B homology models. We performed molecular dynamics simulations to characterize dynamic properties of the PAS-B domain and the generated conformational ensembles were employed in in silico docking. In order to understand structural and ligand binding features we compared the stability and dynamics of the promiscuous AhR PAS-B to other PAS domains exhibiting specific interactions or no ligand binding function. Our exhaustive in silico binding studies, in which we dock a wide spectrum of ligand molecules to the conformational ensembles, suggest that ligand specificity and selection may be determined not only by the PAS-B domain itself, but also by other parts of AhR and its protein interacting partners. We propose that ligand binding pocket and access channels leading to the pocket play equally important roles in discrimination of endogenous molecules and xenobiotics