The ubiquitin-specific protease 21 is critical for cancer cell mitochondrial function and regulates proliferation and migration.

Ubiquitin-specific proteases (USPs) are the main members of deubiquitinases (DUBs) that catalyze removing ubiquitin chains from target proteins, thereby modulating their half-life and function. Enzymatic activity of USP21 regulates protein degradation which is critical for maintaining cell homeostasis. USP21 determines the stability of oncogenic proteins and therefore is implicated in carcinogenesis.

Effective modeling of the chromatin structure by coarse-grained methods.

The interphase chromatin structure is extremely complex, precise and dynamic. Experimental methods can only show the frequency of interaction of the various parts of the chromatin. Therefore, it is extremely important to develop theoretical methods to predict the chromatin structure.

HiCEnterprise: identifying long range chromosomal contacts in Hi-C data.

Motivation: Computational analysis of chromosomal contact data is currently gaining popularity with the rapid advance in experimental techniques providing access to a growing body of data. An important problem in this area is the identification of long range contacts between distinct chromatin regions. Such loops were shown to exist at different scales, either mediating relatively short range interactions between enhancers and promoters or providing interactions between much larger, distant chromosome domains.

QChromosomeVisualizer: A new tool for 3D visualization of long simulations of polymer-like chromosome models.

Recent years have brought us great wealth of new types of experimental data on different aspects of chromatin state, from chromosome conformation assays, through super-resolution microscopic imaging to epigenetic modifications and lamina interaction assays. This rapid increase in data availability have motivated many novel approaches to 3D modeling of chromosomes, their conformations and dynamic behavior. Even though there are many tools already developed for molecular visualization in the field of structural bioinformatics, they are usually optimized for visualization of smaller molecules (like proteins) and much shorter trajectories.

Novel inhibitors of the rRNA ErmC' methyltransferase to block resistance to macrolides, lincosamides, streptogramine B antibiotics.

In erythromycin-resistant bacteria, the N6 position of A2058 in 23S rRNA is mono- or dimethylated by Erm family methyltransferases. This modification results in cross-resistance to macrolides, lincosamides and streptogramin B. Most inhibitors of Erm methyltransferases developed up-to-date target the cofactor-binding pocket, resulting in a lack of selectivity whereas inhibitors that bind the substrate-binding pocket demonstrate low in vitro activity.

Endothelial cell differentiation is encompassed by changes in long range interactions between inactive chromatin regions.

Endothelial cells (ECs) differentiate from mesodermal progenitors during vasculogenesis. By comparing changes in chromatin interactions between human umbilical vein ECs, embryonic stem cells and mesendoderm cells, we identified regions exhibiting EC-specific compartmentalization and changes in the degree of connectivity within topologically associated domains (TADs). These regions were characterized by EC-specific transcription, binding of lineage-determining transcription factors and cohesin.

Modeling of Protein-RNA Complex Structures Using Computational Docking Methods.

A significant part of biology involves the formation of RNA-protein complexes. X-ray crystallography has added a few solved RNA-protein complexes to the repertoire; however, it remains challenging to capture these complexes and often only the unbound structures are available. This has inspired a growing interest in finding ways to predict these RNA-protein complexes.

NPDock: a web server for protein-nucleic acid docking.

Protein-RNA and protein-DNA interactions play fundamental roles in many biological processes. A detailed understanding of these interactions requires knowledge about protein-nucleic acid complex structures. Because the experimental determination of these complexes is time-consuming and perhaps futile in some instances, we have focused on computational docking methods starting from the separate structures.

Computational modeling of protein-RNA complex structures.

Protein-RNA interactions play fundamental roles in many biological processes, such as regulation of gene expression, RNA splicing, and protein synthesis. The understanding of these processes improves as new structures of protein-RNA complexes are solved and the molecular details of interactions analyzed. However, experimental determination of protein-RNA complex structures by high-resolution methods is tedious and difficult.

Sequence-specific cleavage of the RNA strand in DNA-RNA hybrids by the fusion of ribonuclease H with a zinc finger.

Ribonucleases (RNases) are valuable tools applied in the analysis of RNA sequence, structure and function. Their substrate specificity is limited to recognition of single bases or distinct secondary structures in the substrate. Currently, there are no RNases available for purely sequence-dependent fragmentation of RNA.

Crystal structures of the tRNA:m2G6 methyltransferase Trm14/TrmN from two domains of life.

Methyltransferases (MTases) form a major class of tRNA-modifying enzymes needed for the proper functioning of tRNA. Recently, RNA MTases from the TrmN/Trm14 family that are present in Archaea, Bacteria and Eukaryota have been shown to specifically modify tRNA(Phe) at guanosine 6 in the tRNA acceptor stem. Here, we report the first X-ray crystal structures of the tRNA m(2)G6 (N(2)-methylguanosine) MTase (TTC)TrmN from Thermus thermophilus and its ortholog (Pf)Trm14 from Pyrococcus furiosus.

RNA-Puzzles: a CASP-like evaluation of RNA three-dimensional structure prediction.

We report the results of a first, collective, blind experiment in RNA three-dimensional (3D) structure prediction, encompassing three prediction puzzles. The goals are to assess the leading edge of RNA structure prediction techniques; compare existing methods and tools; and evaluate their relative strengths, weaknesses, and limitations in terms of sequence length and structural complexity. The results should give potential users insight into the suitability of available methods for different applications and facilitate efforts in the RNA structure prediction community in ongoing efforts to improve prediction tools.

Computational methods for prediction of protein-RNA interactions.

Understanding the molecular mechanism of protein-RNA recognition and complex formation is a major challenge in structural biology. Unfortunately, the experimental determination of protein-RNA complexes by X-ray crystallography and nuclear magnetic resonance spectroscopy (NMR) is tedious and difficult. Alternatively, protein-RNA interactions can be predicted by computational methods.

DARS-RNP and QUASI-RNP: new statistical potentials for protein-RNA docking.

Background: Protein-RNA interactions play fundamental roles in many biological processes. Understanding the molecular mechanism of protein-RNA recognition and formation of protein-RNA complexes is a major challenge in structural biology. Unfortunately, the experimental determination of protein-RNA complexes is tedious and difficult, both by X-ray crystallography and NMR.

FILTREST3D: discrimination of structural models using restraints from experimental data.

Summary: Automatic methods for macromolecular structure prediction (fold recognition, de novo folding and docking programs) produce large sets of alternative models. These large model sets often include many native-like structures, which are often scored as false positives. Such native-like models can be more easily identified based on data from experimental analyses used as structural restraints (e.

Predicting atomic details of the unfolding pathway for YibK, a knotted protein from the SPOUT superfamily.

Several protein structures have been reported to contain intricate knots of the polypeptide backbone but the mechanism of the (un)folding process of knotted proteins remains unknown. The members of the SPOUT superfamily of RNA methyltransferases are some of the most intensely studied systems for investigation of the knot formation and function. YibK (whose biochemical function remains unknown) is the representative protein of the SPOUT superfamily.

The structure of M.EcoKI Type I DNA methyltransferase with a DNA mimic antirestriction protein.

Type-I DNA restriction-modification (R/M) systems are important agents in limiting the transmission of mobile genetic elements responsible for spreading bacterial resistance to antibiotics. EcoKI, a Type I R/M enzyme from Escherichia coli, acts by methylation- and sequence-specific recognition, leading to either methylation of DNA or translocation and cutting at a random site, often hundreds of base pairs away. Consisting of one specificity subunit, two modification subunits, and two DNA translocase/endonuclease subunits, EcoKI is inhibited by the T7 phage antirestriction protein ocr, a DNA mimic.

PROTMAP2D: visualization, comparison and analysis of 2D maps of protein structure.

Motivation: Protein structure comparison is a fundamental problem in structural biology and bioinformatics. Two-dimensional maps of distances between residues in the structure contain sufficient information to restore the 3D representation, while maps of contacts reveal characteristic patterns of interactions between secondary and super-secondary structures and are very attractive for visual analysis. The overlap of 2D maps of two structures can be easily calculated, providing a sensitive measure of protein structure similarity.

THUMP from archaeal tRNA:m22G10 methyltransferase, a genuine autonomously folding domain.

The tRNA:m2(2)G10 methyltransferase of Pyrococus abyssi (PAB1283, a member of COG1041) catalyzes the N2,N2-dimethylation of guanosine at position 10 in tRNA. Boundaries of its THUMP (THioUridine synthases, RNA Methyltransferases and Pseudo-uridine synthases)--containing N-terminal domain [1-152] and C-terminal catalytic domain [157-329] were assessed by trypsin limited proteolysis. An inter-domain flexible region of at least six residues was revealed.