András Aszódi

• PhD
• Scientific Training Officer at Vienna Biocenter Core Facilities GmbH, Vienna, Austria

We present the MULTOVL application suite that detects and statistically analyses multiple overlaps of genomic regions in a fast and efficient manner. The package supports the detection of multiple region intersections, unions and ‘solitary’ genomic regions. The significance of actually observed overlaps is estimated by comparing them with empirical...

Non-coding (nc) RNAs are involved both in recruitment of vertebrate Polycomb (PcG) proteins to chromatin, and in activation of PcG target genes. Here we investigate dynamic changes in the relationship between ncRNA transcription and recruitment of PcG proteins to chromatin during differentiation. Profiling of purified cell populations from differen...

In mammals, genome-wide chromatin maps and immunofluorescence studies show that broad domains of repressive histone modifications are present on pericentromeric and telomeric repeats and on the inactive X chromosome. However, only a few autosomal loci such as silent Hox gene clusters have been shown to lie in broad domains of repressive histone mod...

We have studied the sampling performance of conformational search programs using geometric and energetic criteria. Ideally, a conformational search algorithm should identify the largest possible number of low-energy structures (energy criterion) covering the widest possible range of molecular shapes (geometric criterion). Geometric analysis consist...

To avoid side effects, it is often desirable to increase the specificity of a drug candidate when targeting one member of a family of related proteins, whereby one exploits small differences between the structures of the binding sites. Identification of such differences can be carried out by analyzing the distributions of physicochemical properties...

Approximately 3 000 genes are regulated in a time-, tissue-, and stimulus-dependent manner by degradation or stabilization of their mRNAs. The process is mediated by interaction of AU-rich elements (AREs) in the mRNA's 3'-untranslated regions with trans-acting factors. AU-rich element-controlled genes of fundamentally different functional relevance...

Analysis of the distributions of physicochemical properties mapped onto molecular surfaces can highlight important similarities or differences between compound classes, contributing to rational drug design efforts. Here we present an approach that uses maximal common subgraph comparison and harmonic shape image matching to detect locally similar re...

Polypeptide α-carbon backbones were modeled as freely rotating chains made up of spherical monomers. The monomers were assigned an abstract binary “hydrophobicity” property that could be either present or absent. Under the assumption that “hydrophobic” residues tend to cluster together, away from the polar solvent, three-dimensional conformations o...

For treatment of skin diseases with topical drugs, penetration of the agents into the relevant layers of the skin is required. Permeation through the skin should, however, be kept to a minimum, in order to avoid the risk of systemic side effects. Here we compared the in vitro skin penetration and permeation of two novel drugs used in the therapy of...

Using a geometric perspective, Protein Geometry, Classification, Topology, and Symmetry reviews and analyzes the structural principals of proteins with the goal of revealing the underlying regularities in their construction. It also reviews computer methods for structure analysis and the automatic comparison and classification of these structures w

A parallel version of an optimization algorithm for arbitrary functions of arbitrary dimension N has been developed and tested on an IBM-Regatta HPC system equipped with 16 CPUs of Power4 type, each with 1.3 GHz clock frequency. The optimization algorithm follows a simplex-like stochastic search technique aimed at quasi-complete sampling of all the...

Gene products differentially expressed in healthy vs. diseased tissues may be considered drug targets since the change in their expression level can be related to the cause and progression of the disease studied. A significant portion of the proteins produced by these genes will be unknown and consequently their function must be characterised. The...

We have designed an improved method for solving the embedding problem, which consists in generating molecular conformations satisfying prescribed distance restraints. The problem was broken up into smaller subproblems by carrying out separate embeddings of subsets of the original point set. The relative orientation of the subsets were then determin...

The application of homology modeling is often limited by the lack of known structures with sufficiently high sequence similarity to the target protein. The recent development of threading methods now enable the identification of likely folding patterns in a number of cases where the structural relatedness between target and template(s) is not detec...

A distance geometry based protein modelling algorithm is presented which relies on the projection of simple model chain coordinates into Euclidean spaces with gradually decreasing dimensionality. Fast embedding was achieved by performing separate distance matrix projections on subsets of the model points. Structural equivalences between the unknown...

Unknown protein structures can be predicted from known structures (the scaffolds) with sequences sufficiently homologous to that of the target, based on the observation that similar sequences usually adopt the same fold. When structural equivalences between residues in the scaffold and target proteins are expressed in terms of conserved interatomic...

A protein sequence is described that consists of a highly repeated 11-mer motif. The motif has the characteristics of an α-helical coilled-coil but contains, in addition, a highly conserved histidine position that lies centrally on the hydrophobic face of the amphipathic helix. The sequence was modelled as either a three or four stranded coilled-co...

We have designed a distance geometry-based method for obtaining the tertiary fold of a protein from a limited number of structure-specific distance restraints and the secondary structure assignment. Interresidue distances were predicted from patterns of conserved hydrophobic amino acids deduced from multiple alignments. A simple model chain represe...

The hydrophobic amino acids that make up the core of a protein can be expected to be closer together than the rest of the residues in the molecule and are likely to remain conserved during evolution due to their important role. In the present study, a general theoretical framework is provided for estimating interresidue distances from residue hydro...

Model polypeptide chains were folded into 3-D compact conformations using distance geometry techniques. Interresidue distances were predicted from the hydrophobicity of the monomers and were refined by repeated projections into lower-dimensional spaces. Main-chain hydrogen bond networks were constructed and propagated through the structure by adjus...

Calpain activity of nerve growth factor (NGF)-induced rat pheochromocytoma (PC12) cells shows a transient diminution in the early phase of differentiation. Calpain activity can be further decreased by a cell-permeable calpain inhibitor, calpeptin, which enhances the effect of NGF by stimulating neurite elongation. The number of neurites sprouted by...

A known protein structure can be modified and manipulated to produce a model for another protein with which it shares some sequence similarity. Typical changes involve the substitution and reorientation of side chains and the remodeling of the main chain to accommodate possible insertions and deletions of sequences. Where the two sequences are clea...

One-dimensional amino acid sequences and three-dimensional folded polypeptide chains were modelled as non-directed graphs in which nodes corresponded to amino acids and arcs repre sented connections between them. In the case of folded chains, non-backbone connections were assigned to amino acid pairs if their distance was lower than a threshold. Tw...

The mechanisms of action and physiological functions of two calcium-activated enzyme families, the calpains and transglutaminases, are discussed: 1. Both enzymes work via a covalent acylenzyme intermediate. Calpains, as other papain-like proteases, have a Cys and His residue in the active site, which in the ground state tend to form a thiolate-imid...

The dynamics of N-methyl-D-aspartate receptor blockade-induced transitions between two types of intracellularly recorded spontaneous membrane potential oscillation from cat thalamic neurons have been studied using non-linear dynamics techniques. We report that, as previously predicted by theoretical studies, the number of degrees of freedom of thes...

Microtubule-associated protein 2 (MAP2), a long, filamentous molecule thought to cross-link dendritic cytoskeleton, is rich in PEST sequences, putative signals for rapid proteolytic degradation. It is suggested that MAP2 is indeed highly susceptible to protease, e.g. calpain, attack, which is needed for a plastic change, but actual breakdown depend...

The response of a reaction network composed of protein kinase A, calpain, and protein phosphatase to transient cAMP and Ca2+ signals was studied. An essential feature of signal convergence is that the regulatory subunit of cAMP-dissociated protein kinase A undergoes limited proteolysis by the Ca(2+)-activated proteinase calpain. A dynamic model of...

Three molecular (enzyme) kinetic models have been designed that exhibit the basic properties of associative learning (classical conditioning). The enzyme systems are acted upon by an 'unconditioned' and a 'conditioned' ligand: temporally paired application of the two ligands leads to covalent enzyme modification, which serves as 'memory trace'. The...