The application of cluster analysis in the intercomparison of loop structures in RNA

We have developed a computational approach for the comparison and classification of RNA loop structures. Hairpin or interior loops identified in atomic resolution RNA structures were intercompared by conformational matching. The root-mean-square deviation (RMSD) values between all pairs of RNA fragments of interest, even if from different molecules, are calculated. Subsequently, cluster analysis is performed on the resulting matrix of RMSD distances using the unweighted pair group method with arithmetic mean (UPGMA). The cluster analysis objectively reveals groups of folds that resemble one another. To demonstrate the utility of the approach, a comprehensive analysis of all the terminal hairpin tetraloops that have been observed in 15 RNA structures that have been determined by X-ray crystallography was undertaken. The method found major clusters corresponding to the well-known GNRA and UNCG types. In addition, two tetraloops with the unusual primary sequence UMAC (M is A or C) were successfully assigned to the GNRA cluster. Larger loop structures were also examined and the clustering results confirmed the occurrence of variations of the GNRA and UNCG tetraloops in these loops and provided a systematic means for locating them. Nineteen examples of larger loops that closely resemble either the GNRA or UNCG tetraloop were found in the large ribosomal RNAs. When the clustering approach was extended to include all structures in the SCOR database, novel relationships were detected including one between the ANYA motif and a less common folding of the GAAA tetraloop sequence.     

The role of risk subcortical brain regions in the formation alalie

Complex children examination with alalia was based the analysis by the role of subcortical brain structures for the formation of speech was investigated. Alalia is systemic speech underdevelopment in children, which violated all the components of speech. Evaluation of the functional state of brain structures on the EEG has allowed to distinguish the two groups, which depend on the nature of changes in bioelectric activity (BEA). The first group is one with the changes of alpha rhythm and/or local changes in BEA predominantly in the left hemisphere, the second group with violations ofbrainstem origin, mainly generalized EEG changes. A comprehensive analysis of clinical data has allowed to suggest the basis of the formation alalia lies subcortical structures lesion of the left hemisphere of the brain and stem departments of one. The analysis of perinatal risk factors has allowed to hypothesize about the connection of subcortical structures lesion with antenatal complications in the first half of pregnancy.     

Analysis of local helix bending in crystal structures of DNA oligonucleotides and DNA-protein complexes.

Sequence-dependent bending of the helical axes in 112 oligonucleotide duplex crystal structures resident in the Nucleic Acid Database have been analyzed and compared with the use of bending dials, a computer graphics tool. Our analysis includes structures of both A and B forms of DNA and considers both uncomplexed forms of the double helix as well as those bound to drugs and proteins. The patterns in bending preferences in the crystal structures are analyzed by base pair steps, and emerging trends are noted. Analysis of the 66 B-form structures in the Nucleic Acid Database indicates that uniform trends within all pyrimidine-purine and purine-pyrimidine steps are not necessarily observed but are found particularly at CG and GC steps of dodecamers. The results support the idea that AA steps are relatively straight and that larger roll bends occur at or near the junctions of these A-tracts with their flanking sequences. The data on 16 available crystal structures of protein-DNA complexes indicate that the majority of the DNA bends induced via protein binding are sharp localized kinks. The analysis of the 30 available A-form DNA structures indicates that these structures are also bent and show a definitive preference for bending into the deep major groove over the shallow minor groove.     

A study of the occurrence of regulator secondary structures in globular proteins

The distribution of regular secondary structures, viz. α-helices and β-strands, along the length of over 70 properties whose secondary structural details have been reported, has been analysed. The occurrence of these regular structures tends to be a maximum at the N- and C-termini. Our analysis suggests that both these free ends could possibly serve as nucleating centers for secondary structures and could play an important role in the folding of proteins.     

The role of damage to the cerebral subcortical divisions in the formation of alalia

The role of the cerebral subcortical structures in speech formation was studied by analyzing the data on the comprehensive examination of children with alalia. Alalia is a systemic underdevelopment of speech in which all the speech components are disordered. The assessment of the functional state of the brain structures by means of EEG allowed us to identify two groups differing in the pattern of changes in bioelectrical activity (BEA): group 1 with α rhythm changes and/or local BEA changes, predominantly in the left hemisphere, and group 2 with predominantly generalized EEG changes of brainstem origin. Integrated analysis of clinical data allowed us to suggest that a lesion of the left hemisphere subcortical structures and the brainstem divisions underlies the formation of alalia. The analysis of the perinatal risk factors allowed us to advance the hypothesis that damage to the subcortical structures was linked to antenatal complications in the first half of pregnancy.     

The phylogenetic information carried by a new set of morphological characters in planthoppers: the internal mouthpart structures and test in the Cixiidae model (Hemiptera: Fulgoromorpha)

Internal morphological structures of Cixiidae mouthparts are described and compared in various representatives of the Cixiidae and several other representatives of hemipterans. The morphological study shows that the mouthpart structures have not evolved uniformly and reveals the great disparity of these structures. Particularly, the connecting system of the mouthparts, localisation of salivary canal and shape of the mandibular and maxillar stylets provide together a new set of 17 new characters. A parsimonious analysis to evaluate the phylogenetic interest carried by these 17 selected characters shows that mouthpart structures have not evolved anarchically, but that they indeed carry some phylogenetic information that will be useful to be included in further morphological phylogenetic analysis.     

Structural organization of kinetoplast DNA and its compaction in the in vitro model system.

Electron microscopic studies of Leishmania gymnodactyli cells lysed at hypotonic conditions showed that the structures identified as kinetoplast DNA have the appearance of loose accumulations of crossed and sometimes branched rod-like structures 100 to 200 nm long and 20 nm thick. The compaction of isolated kinetoplast DNA (kpDNA) caused by interaction with synthetic tripeptide--dansylhydrazide trivaline--was also studied. The analysis of the structures arising at different steps of compaction showed that the minicircles are compacted forming rod-like structures where minicircle double-stranded DNA segments are closely associated side by side in a manner which was earlier described for initial compaction stages of "triple rings". These rod-like structures resemble in their appearance the structures found in lysed cell preparations obtained according to Miller's method. Branching of rod-like structures can be the consequence of minicircle catenation. In vitro compaction is completed with the formation of a compacted network, its diameter being 3 to 6 times smaller as compared with the initial one.     

信号处理技术在生物分子序列分析中的应用

信号处理技术在生物分子序列分析中的应用主要包括周期分析、基因预测、相似和重复序列分析、蛋白质分子结构预测等。涉及的技术方法有：Fourier变换、小波变换、相关分析、分形技术、非线性信号处理技术等。本文将全面回顾这些应用。     

Analysis of correlated motion in antibody combining sites from molecular dynamics simulations

The crystal structures of the NC6.8-antisweet taste ligand complex and the uncomplexed antibody structures display significant differences in the conformations of residues in the combining site. A molecular dynamics method was employed to understand the flexibility and correlated motion of key combining site residues in the uncomplexed antibody. The simulations reveal that residues that show conformational differences between the complex and uncomplexed structures display strong dynamical correlations. Extensive analysis of the dynamics trajectory using time correlation methods is presented.     

多糖高级结构解析方法的研究进展

研究发现,多糖的生物活性不仅与其一级结构（如分支度、单糖组成及糖苷键连接方式等）有关,而且与其空间结构也密不可分。 因此,对多糖高级结构的研究将有助于阐释其构效关系,为寻找具有生物活性的多糖和开发多糖药物提供理论依据。传统的多糖结构分 析方法具有一定的局限性,已不能满足多糖研究的需求,而现代物理技术的发展则为多糖高级结构解析提供了新的手段。综述近年来多 糖高级结构解析方法的研究进展。     

Pupils' perceptions of three-dimensional structures in biology lessons

An investigation into 11–15 year old pupils' ability to tackle tasks concerned with the understanding of threedimensional structures studied in school biology lessons is outlined. The investigation takes the form ofapaperand- pencil test, and the test items call for the interpretation of sectional views of three-dimensional structures (represented by diagrams and stereograms) studied in conventional biology syllabuses for 11–15 year olds. Test scores were subject to cluster analysis and the emergent groups are described.

The analysis pointed to the existence of two discrete skills used by pupils interpreting three-dimensional structures. These are the skill of abstracting sectional shapes and that of appreciating the spatial relationships of the internal parts of a structure-. Extracts from tape recordings of pupils ‘talking their way through’ selected tasks corroborate the two-skill theory.     

Overcoming a barrier for DNA polymerization in triplex-forming sequences.

Folded structures in the DNA template, such as hairpins and multi-stranded structures, often serve as pause and arrest sites for DNA polymerases. DNA polymerization is particularly difficult on mirror-repeated homopurine.homopyrimidine templates where triple-stranded (triplex) structures may form between the nascent and folded template strands. In order to use a linear PCR amplification approach for the structural analysis of DNA in mirror-repeated sequences we modified a conventional protocol. The barrier for DNA synthesis can be eliminated using an oligonucleotide that hybridizes with the template to prevent its folding and is subsequently displaced by the progressing polymerase. The described approach is potentially useful for sequencing and analysis of chemical adducts and point mutations in a variety of sequences prone to the formation of folded structures, such as long hairpins and quadruplexes.     

Propagation of Turing patterns in a plankton model

The paper is devoted to a reaction-diffusion system of equations describing phytoplankton and zooplankton distributions. Linear stability analysis of the model is carried out. Turing and Hopf stability boundaries are found. Emergence of two-dimensional spatial structures is illustrated by numerical simulations. Travelling waves between various stationary solutions are investigated. Transitions between homogeneous in space stationary solutions and Turing structures are studied.     

Reconstruction of spatial structure of plant protein phosphatase type-1 and -2A in complex with okadaic acid

The homology modeling, based on known temple structures of Homo sapiens protein phosphatase type-1 and -2A was implemented. The spatial structures of the human protein phosphatases and their plant homologs from Arabidopsis thaliana was predicted. The quality of models was confirmed by conformational analysis and root mean square deviations. The sites of okadaic acid binding in molecules of plant protein phosphatases (type-1 and -2A) were proved by the data of comparative analysis and molecular dynamics.     

Characterization of the oligosaccharide structures on recombinant human prorenin expressed in Chinese hamster ovary cells.

Prorenin was isolated by immunoprecipitation from the culture medium of Chinese hamster ovary cells transfected with a human prorenin cDNA. The N-linked oligosaccharide structures on the in vivo [3H]mannose-labeled, purified protein were characterized using a combination of serial lectin affinity chromatography, high-pressure liquid chromatography, ion-exchange chromatography, and size-exclusion chromatography and treatment with specific glycosidases and methylation analysis. Approximately 61% of the oligosaccharides on the molecule are complex type, in the form of tetraantennary (2%), 2,6-branched triantennary (13%), 2,4-branched triantennary (3%), and biantennary (43%) structures. The majority of all complex type structures are core-fucosylated. Sialic acids are linked at the C-3 position of terminal galactose, and the degree of sialylation of the bi- and triantennary structures varies between nonsialylated and fully sialylated; no tetraatennary structure contains more than three sialic acid residues. Recombinant prorenin contains 4% hybrid-type structures, all of which carry a terminal sialic acid residue. The remaining 35% of the structures on the molecule are high mannose type, composed of 5, 6, or 7 mannose residues. Approximately 6% of the high mannose type structures and 10% of the hybrid structures are phosphorylated, as judged by their susceptibility to treatment with alkaline phosphatase. Compositional analysis of an unlabeled preparation of the protein suggested the presence of approximately 1.4 oligosaccharide units per molecule.     

Prediction of Three Dimensional Structure of Calmodulin

Calmodulin (CaM) is an important human protein, which has multiple structures. Numerous researchers studied the CaM structures in the past, and about 50 different structures in complex with fragments derived from CaM-regulated proteins have been discovered. Discovery and analysis of existing and new CaM structures is difficult due to the inherent complexity, i.e. flexibility of 6 loops and a central linker that constitute part of the CaM structure. The extensive interest in CaM structure analysis and discovery calls for a comprehensive study, which based on the accumulated expertise would design a method for prediction and analysis of future and existing CaM structures. It is also important to find the mechanisms by which the protein adjusts its structure with respect to various factors. To this end, this paper analyzes the known CaM structures and finds four factors that influence CaM structure, which include existence of Ca²⁺ binding, different binding segments, measuring surroundings, and sequence mutation. The degree of influence of specific factors on different structural regions is also investigated. Based on the analysis of the relation between the four factors and the corresponding CaM structure a novel method for prediction of the CaM structure in complex with novel segments, given that the surroundings of the complex, is developed. The developed prediction method is tested on a set aside, newest CaM structure. The prediction results provide useful and accurate information about the structure verifying high quality of the proposed prediction method and performed structural analysis.     

Principal components analysis of protein structure ensembles calculated using NMR data

One important problem when calculating structures of biomolecules from NMR data is distinguishing converged structures from outlier structures. This paper describes how Principal Components Analysis (PCA) has the potential to classify calculated structures automatically, according to correlated structural variation across the population. PCA analysis has the additional advantage that it highlights regions of proteins which are varying across the population. To apply PCA, protein structures have to be reduced in complexity and this paper describes two different representations of protein structures which achieve this. The calculated structures of a 28 amino acid peptide are used to demonstrate the methods. The two different representations of protein structure are shown to give equivalent results, and correct results are obtained even though the ensemble of structures used as an example contains two different protein conformations. The PCA analysis also correctly identifies the structural differences between the two conformations.     

Distribution of sex chromosomes in dysgenetic gonads of mixed type

In a four-week-old child with female external and internal genitalia but with clitoris hypertrophy chromosome analysis from blood lymphocytes revealed a 46,XY karyotype. No deletion of Y chromosomal sequences was detected by PCR analysis of genomic DNA isolated from peripheral blood leucocytes. Because of the increased risk for gonadal tumours, gonadectomy was performed. Conventional cytogenetic analysis of the left dysgenetic gonad revealed a gonosomal mosaicism with a 45,X cell line in 27 of 50 metaphases. The dysgenetic left gonad demonstrated a significantly higher proportion (P = 0.005) of cells carrying a Y chromosome (46.3%) than the streak gonad from the right side (33.9%). Histomorphological examination of the left gonad revealed immature testicular tissue and rete-like structures as well as irregular ovarian type areas with cystic follicular structures. Interphase FISH analysis of the different tissues of this dysgenetic gonad demonstrated variable proportions of cells with an X and a Y chromosome. Whereas Sertoli cells and rete-like structures revealed a significantly higher proportion of XY cells in relation to the whole section of the dysgenetic gonad (P < 0.0001), almost all granulose-like cells carried no Y chromosome. The proportion of XY/X cells in theca-like cells and Leydig cells was similar to that of the whole dysgenetic gonad. In contrast to these findings, spermatogonia exclusively contained an XY constellation.     

Experimental evidence for the correlation of bond distances in peptide groups detected in ultrahigh-resolution protein structures

The structural analysis of a deamidated derivative of ribonuclease A, determined at 0.87 A resolution, reveals a highly significant negative correlation between CN and CO bond distances in peptide groups. This trend, i.e. the CO bond lengthens when the CN bond shortens, is also found in seven out of eight protein structures, determined at ultrahigh resolution (<0.95 A). In five of them the linear correlation is statistically significant at the 95% confidence level. The present findings are consistent with the traditional view of amide resonance and, although already found in small peptide structures, they represent a new and important result. In fact, in a protein structure the fine details of the peptide geometry are only marginally affected by the crystal field and they are mostly produced by intramolecular and solvent interactions. The analysis of very high-resolution protein structures can reveal subtle information about local electronic features of proteins which may be critical to folding, function or ligand binding.