This paper presents the utilization of progressive alignment principle for positional adjustment of a set of genomic signals with different lengths. The new method of multiple alignment of signals based on dynamic time warping is tested for the purpose of evaluating the similarity of different length genes in phylogenetic studies. Two sets of phylogenetic markers were used to demonstrate the effectiveness of the evaluation of intraspecies and interspecies genetic variability. The part of the proposed method is modification of pairwise alignment of two signals by dynamic time warping with using correlation in a sliding window. The correlation based dynamic time warping allows more accurate alignment dependent on local homologies in sequences without the need of scoring matrix or evolutionary models, because mutual similarities of residues are included in the numerical code of signals.
- MeSH
- Algorithms MeSH
- RNA, Bacterial genetics MeSH
- Species Specificity MeSH
- Phylogeny MeSH
- Genome, Bacterial * MeSH
- Genomics methods MeSH
- Signal Processing, Computer-Assisted MeSH
- RNA, Ribosomal, 18S genetics MeSH
- Sequence Alignment methods MeSH
- Computational Biology methods MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
In this paper, we present a novel algorithm for measuring protein similarity based on their 3-D structure (protein tertiary structure). The algorithm used a suffix tree for discovering common parts of main chains of all proteins appearing in the current research collaboratory for structural bioinformatics protein data bank (PDB). By identifying these common parts, we build a vector model and use some classical information retrieval (IR) algorithms based on the vector model to measure the similarity between proteins--all to all protein similarity. For the calculation of protein similarity, we use term frequency × inverse document frequency ( tf × idf ) term weighing schema and cosine similarity measure. The goal of this paper is to introduce new protein similarity metric based on suffix trees and IR methods. Whole current PDB database was used to demonstrate very good time complexity of the algorithm as well as high precision. We have chosen the structural classification of proteins (SCOP) database for verification of the precision of our algorithm because it is maintained primarily by humans. The next success of this paper would be the ability to determine SCOP categories of proteins not included in the latest version of the SCOP database (v. 1.75) with nearly 100% precision.
- MeSH
- Algorithms MeSH
- Data Mining methods MeSH
- Databases, Protein MeSH
- Humans MeSH
- Proteins chemistry MeSH
- Reproducibility of Results MeSH
- Structural Homology, Protein MeSH
- Protein Structure, Tertiary MeSH
- Artificial Intelligence MeSH
- Computational Biology methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Acetabulum surgery physiopathology MeSH
- Surgery, Computer-Assisted methods instrumentation trends MeSH
- Humans MeSH
- Minimally Invasive Surgical Procedures methods statistics & numerical data MeSH
- Arthroplasty, Replacement, Hip methods statistics & numerical data MeSH
- Outcome and Process Assessment, Health Care methods statistics & numerical data MeSH
- Check Tag
- Humans MeSH
- Publication type
- Comparative Study MeSH
A wealth of evidence provides support for magnetic alignment (MA) behavior in a variety of disparate species within the animal kingdom, in which an animal, or a group of animals, show a tendency to align the body axis in a consistent orientation relative to the geomagnetic field lines. Interestingly, among vertebrates, MA typically coincides with the north-south magnetic axis, however, the mean directional preferences of an individual or group of organisms is often rotated clockwise from the north-south axis. We hypothesize that this shift is not a coincidence, and future studies of this subtle, yet consistent phenomenon may help to reveal some properties of the underlying sensory or processing mechanisms, that, to date, are not well understood. Furthermore, characterizing the fine structure exhibited in MA behaviors may provide key insights to the biophysical substrates mediating magnetoreception in vertebrates. Therefore, in order to determine if a consistent shift is exhibited in taxonomically diverse vertebrates, we performed a meta-analysis on published MA datasets from 23 vertebrate species that exhibited an axial north-south preference. This analysis revealed a significant clockwise shift from the north-south magnetic axis. We summarize and discuss possible competing hypotheses regarding the proximate mechanisms underlying the clockwise shifted MA and conclude that the most likely cause of such a shift would be a lateralization in central processing of magnetic information.
- MeSH
- Species Specificity MeSH
- Functional Laterality physiology MeSH
- Magnetic Phenomena * MeSH
- Vertebrates physiology MeSH
- Orientation * MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
Tuberculosis, the second leading infectious disease killer after HIV, remains a top public health priority. The causative agent of tuberculosis, Mycobacterium tuberculosis (Mtb), which can cause both acute and clinically latent infections, reprograms metabolism in response to the host niche. Phosphoenolpyruvate carboxykinase (Pck) is the enzyme at the center of the phosphoenolpyruvate-pyruvate-oxaloacetate node, which is involved in regulating the carbon flow distribution to catabolism, anabolism, or respiration in different states of Mtb infection. Under standard growth conditions, Mtb Pck is associated with gluconeogenesis and catalyzes the metal-dependent formation of phosphoenolpyruvate. In non-replicating Mtb, Pck can catalyze anaplerotic biosynthesis of oxaloacetate. Here, we present insights into the regulation of Mtb Pck activity by divalent cations. Through analysis of the X-ray structure of Pck-GDP and Pck-GDP-Mn2+ complexes, mutational analysis of the GDP binding site, and quantum mechanical (QM)-based analysis, we explored the structural determinants of efficient Mtb Pck catalysis. We demonstrate that Mtb Pck requires presence of Mn2+ and Mg2+ cations for efficient catalysis of gluconeogenic and anaplerotic reactions. The anaplerotic reaction, which preferably functions in reducing conditions that are characteristic for slowed or stopped Mtb replication, is also effectively activated by Fe2+ in the presence of Mn2+ or Mg2+ cations. In contrast, simultaneous presence of Fe2+ and Mn2+ or Mg2+ inhibits the gluconeogenic reaction. These results suggest that inorganic ions can contribute to regulation of central carbon metabolism by influencing the activity of Pck. Furthermore, the X-ray structure determination, biochemical characterization, and QM analysis of Pck mutants confirmed the important role of the Phe triad for proper binding of the GDP-Mn2+ complex in the nucleotide binding site and efficient catalysis of the anaplerotic reaction.
- MeSH
- Enzyme Activation MeSH
- Phosphoenolpyruvate Carboxykinase (ATP) chemistry genetics metabolism MeSH
- Gluconeogenesis MeSH
- Catalysis MeSH
- Cations, Divalent MeSH
- Kinesis MeSH
- Protein Conformation MeSH
- Humans MeSH
- Models, Molecular MeSH
- Molecular Sequence Data MeSH
- Protein Multimerization MeSH
- Mutation MeSH
- Mycobacterium tuberculosis enzymology genetics MeSH
- Nucleotides metabolism MeSH
- Amino Acid Sequence MeSH
- Sequence Alignment MeSH
- Binding Sites MeSH
- Hydrogen Bonding MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Pelvic floor muscles have potential to influence relative pelvic alignment. Side asymmetry in pelvic floor muscle tension is claimed to induce pelvic malalignment. However, its nature and amplitude are not clear. There is a need for non-invasive and reliable assessment method. An intervention experiment of unilateral pelvic floor muscle activation on healthy females was performed using image data for intra-subject comparison of normal and altered configuration of bony pelvis. METHODS: Sequent magnetic resonance imaging of 14 females in supine position was performed with 1.5 T static body coil in coronal orientation. The intervention, surface functional electrostimulation, was applied to activate pelvic floor muscles on the right side. Spatial coordinates of 23 pelvic landmarks were localized in each subject and registered by specially designed magnetic resonance image data processing tool (MPT2006), where individual error calculation; data registration, analysis and 3D visualization were interfaced. FINDINGS: The effect of intervention was large (Cohen's d=1.34). We found significant differences in quantity (P<0.01) and quality (P=0.02) of normal and induced pelvic displacements. After pelvic floor muscle activation on the right side, pelvic structures shifted most frequently to the right side in ventro-caudal direction. The right femoral head, the right innominate and the coccyx showed the largest displacements. INTERPRETATION: The consequences arising from the capacity of pelvic floor muscles to displace pelvic bony structures are important to consider not only in management of malalignment syndrome but also in treatment of incontinence. The study has demonstrated benefits associated with processing of magnetic resonance image data within pelvic region with high localization and registration reliability.
- MeSH
- Adult MeSH
- Image Interpretation, Computer-Assisted methods MeSH
- Muscle, Skeletal anatomy & histology MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Pelvis anatomy & histology MeSH
- Pelvic Floor anatomy & histology MeSH
- Subtraction Technique MeSH
- Image Enhancement methods MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
Receptor proteins at the cell surface regulate the ability of natural killer cells to recognize and kill a variety of aberrant target cells. The structural features determining the function of natural killer receptor proteins 1 (NKR-P1s) are largely unknown. In the present work, refined homology models are generated for the C-type lectin-like extracellular domains of rat NKR-P1A and NKR-P1B, mouse NKR-P1A, NKR-P1C, NKR-P1F, and NKR-P1G, and human NKR-P1 receptors. Experimental data on secondary structure, tertiary interactions, and thermal transitions are acquired for four of the proteins using Raman and infrared spectroscopy. The experimental and modeling results are in agreement with respect to the overall structures of the NKR-P1 receptor domains, while suggesting functionally significant local differences among species and isoforms. Two sequence regions that are conserved in all analyzed NKR-P1 receptors do not correspond to conserved structural elements as might be expected, but are represented by loop regions, one of which is arranged differently in the constructed models. This region displays high flexibility but is anchored by conserved sequences, suggesting that its position relative to the rest of the domain might be variable. This loop may contribute to ligand-binding specificity via a coupled conformational transition.
- MeSH
- Amino Acid Motifs MeSH
- Phylogeny MeSH
- Conserved Sequence MeSH
- Rats MeSH
- NK Cell Lectin-Like Receptor Subfamily B chemistry classification MeSH
- Humans MeSH
- Molecular Sequence Data MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Spectrum Analysis, Raman MeSH
- Amino Acid Sequence MeSH
- Sequence Alignment MeSH
- Molecular Dynamics Simulation MeSH
- Spectroscopy, Fourier Transform Infrared MeSH
- Structural Homology, Protein MeSH
- Protein Structure, Tertiary MeSH
- Thermodynamics MeSH
- Binding Sites MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Pepsin-family aspartic peptidases are biosynthesized as inactive zymogens in which the propeptide blocks the active site until its proteolytic removal upon enzyme activation. Here, we describe a novel dual regulatory function for the propeptide using a set of crystal structures of the parasite cathepsin D IrCD1. In the IrCD1 zymogen, intramolecular autoinhibition by the intact propeptide is mediated by an evolutionarily conserved exosite on the enzyme core. After activation, the mature enzyme employs the same exosite to rebind a small fragment derived from the cleaved propeptide. This fragment functions as an effective natural inhibitor of mature IrCD1 that operates in a pH-dependent manner through a unique allosteric inhibition mechanism. The study uncovers the propeptide-binding exosite as a target for the regulation of pepsin-family aspartic peptidases and defines the structural requirements for exosite inhibition.
- MeSH
- Enzyme Activation MeSH
- Allosteric Regulation MeSH
- Catalytic Domain MeSH
- Cathepsin D chemistry metabolism MeSH
- Kinetics MeSH
- Ticks enzymology MeSH
- Hydrogen-Ion Concentration MeSH
- Crystallography, X-Ray MeSH
- Ligands MeSH
- Peptides chemistry metabolism MeSH
- Enzyme Precursors chemistry metabolism MeSH
- Amino Acid Sequence MeSH
- Sequence Alignment MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Heteronuclear and homonuclear direct (D) and indirect (J) spin-spin interactions are important sources of structural information about nucleic acids (NAs). The Hamiltonians for the D and J interactions have the same functional form; thus, the experimentally measured apparent spin-spin coupling constant corresponds to a sum of J and D. In biomolecular NMR studies, it is commonly presumed that the dipolar contributions to Js are effectively canceled due to random molecular tumbling. However, in strong magnetic fields, such as those employed for NMR analysis, the tumbling of NA fragments is anisotropic because the inherent magnetic susceptibility of NAs causes an interaction with the external magnetic field. This motional anisotropy is responsible for non-zero D contributions to Js. Here, we calculated the field-induced D contributions to 33 structurally relevant scalar coupling constants as a function of magnetic field strength, temperature and NA fragment size. We identified two classes of Js, namely (1)JCH and (3)JHH couplings, whose quantitative interpretation is notably biased by NA motional anisotropy. For these couplings, the magnetic field-induced dipolar contributions were found to exceed the typical experimental error in J-coupling determinations by a factor of two or more and to produce considerable over- or under-estimations of the J coupling-related torsion angles, especially at magnetic field strengths >12 T and for NA fragments longer than 12 bp. We show that if the non-zero D contributions to J are not properly accounted for, they might cause structural artifacts/bias in NA studies that use solution NMR spectroscopy.
