787 research outputs found
Recoverable One-dimensional Encoding of Three-dimensional Protein Structures
Protein one-dimensional (1D) structures such as secondary structure and
contact number provide intuitive pictures to understand how the native
three-dimensional (3D) structure of a protein is encoded in the amino acid
sequence. However, it has not been clear whether a given set of 1D structures
contains sufficient information for recovering the underlying 3D structure.
Here we show that the 3D structure of a protein can be recovered from a set of
three types of 1D structures, namely, secondary structure, contact number and
residue-wise contact order which is introduced here for the first time. Using
simulated annealing molecular dynamics simulations, the structures satisfying
the given native 1D structural restraints were sought for 16 proteins of
various structural classes and of sizes ranging from 56 to 146 residues. By
selecting the structures best satisfying the restraints, all the proteins
showed a coordinate RMS deviation of less than 4\AA{} from the native
structure, and for most of them, the deviation was even less than 2\AA{}. The
present result opens a new possibility to protein structure prediction and our
understanding of the sequence-structure relationship.Comment: Corrected title. No Change In Content
Properties of contact matrices induced by pairwise interactions in proteins
The total conformational energy is assumed to consist of pairwise interaction
energies between atoms or residues, each of which is expressed as a product of
a conformation-dependent function (an element of a contact matrix, C-matrix)
and a sequence-dependent energy parameter (an element of a contact energy
matrix, E-matrix). Such pairwise interactions in proteins force native
C-matrices to be in a relationship as if the interactions are a Go-like
potential [N. Go, Annu. Rev. Biophys. Bioeng. 12. 183 (1983)] for the native
C-matrix, because the lowest bound of the total energy function is equal to the
total energy of the native conformation interacting in a Go-like pairwise
potential. This relationship between C- and E-matrices corresponds to (a) a
parallel relationship between the eigenvectors of the C- and E-matrices and a
linear relationship between their eigenvalues, and (b) a parallel relationship
between a contact number vector and the principal eigenvectors of the C- and
E-matrices; the E-matrix is expanded in a series of eigenspaces with an
additional constant term, which corresponds to a threshold of contact energy
that approximately separates native contacts from non-native ones. These
relationships are confirmed in 182 representatives from each family of the SCOP
database by examining inner products between the principal eigenvector of the
C-matrix, that of the E-matrix evaluated with a statistical contact potential,
and a contact number vector. In addition, the spectral representation of C- and
E-matrices reveals that pairwise residue-residue interactions, which depends
only on the types of interacting amino acids but not on other residues in a
protein, are insufficient and other interactions including residue
connectivities and steric hindrance are needed to make native structures the
unique lowest energy conformations.Comment: Errata in DOI:10.1103/PhysRevE.77.051910 has been corrected in the
present versio
Predicting Secondary Structures, Contact Numbers, and Residue-wise Contact Orders of Native Protein Structure from Amino Acid Sequence by Critical Random Networks
Prediction of one-dimensional protein structures such as secondary structures
and contact numbers is useful for the three-dimensional structure prediction
and important for the understanding of sequence-structure relationship. Here we
present a new machine-learning method, critical random networks (CRNs), for
predicting one-dimensional structures, and apply it, with position-specific
scoring matrices, to the prediction of secondary structures (SS), contact
numbers (CN), and residue-wise contact orders (RWCO). The present method
achieves, on average, accuracy of 77.8% for SS, correlation coefficients
of 0.726 and 0.601 for CN and RWCO, respectively. The accuracy of the SS
prediction is comparable to other state-of-the-art methods, and that of the CN
prediction is a significant improvement over previous methods. We give a
detailed formulation of critical random networks-based prediction scheme, and
examine the context-dependence of prediction accuracies. In order to study the
nonlinear and multi-body effects, we compare the CRNs-based method with a
purely linear method based on position-specific scoring matrices. Although not
superior to the CRNs-based method, the surprisingly good accuracy achieved by
the linear method highlights the difficulty in extracting structural features
of higher order from amino acid sequence beyond that provided by the
position-specific scoring matrices.Comment: 20 pages, 1 figure, 5 tables; minor revision; accepted for
publication in BIOPHYSIC
Wang-Landau molecular dynamics technique to search for low-energy conformational space of proteins
Multicanonical molecular dynamics (MD) is a powerful technique for sampling
conformations on rugged potential surfaces such as protein. However, it is
notoriously difficult to estimate the multicanonical temperature effectively.
Wang and Landau developed a convenient method for estimating the density of
states based on a multicanonical Monte Carlo method. In their method, the
density of states is calculated autonomously during a simulation. In this paper
we develop a set of techniques to effectively apply the Wang-Landau method to
MD simulations. In the multicanonical MD, the estimation of the derivative of
the density of states is critical. In order to estimate it accurately, we
devise two original improvements. First, the correction for the density of
states is made smooth by using the Gaussian distribution obtained by a short
canonical simulation. Second, an approximation is applied to the derivative,
which is based on the Gaussian distribution and the multiple weighted histogram
technique. A test of this method was performed with small polypeptides,
Met-enkephalin and Trp-cage, and it is demonstrated that Wang-Landau MD is
consistent with replica exchange MD but can sample much larger conformational
space.Comment: 8 pages, 7 figures, accepted for publication in Physical Review
Ultrastructural study of the effects of tranexamic acid and urokinase on metastasis of Lewis lung carcinoma.
Lewis lung carcinoma cells were implanted in the foot-pads of mice and the effects of the plasminogen-plasmin inhibitor tranexamic acid (t-AMCHA) and of the plasminogen activator urokinase on metastasis were examined by electron microscopy. The intravascular tumour cells were not associated with thrombus formation in either control or urokinase-treated mice. Polymerized fibrin deposition around tumour cells and thrombi composed of fibrin and platelets was observed only in the mice given t-AMCHA. This suggests that the inhibition of fibrinolysis by tACC caused fibrin deposition and thrombus formation around intravascular tumour cells, which prevented release of the cells from primary foci to form secondary tumours. On the other hand, fibrinolysis induced by urokinase prevented thrombus formation, and accelerated cell release from primary foci
Fast and efficient critical state modelling of field-cooled bulk high-temperature superconductors using a backward computation method
Abstract: A backward computation method has been developed to accelerate modelling of the critical state magnetization current in a staggered-array bulk high-temperature superconducting (HTS) undulator. The key concept is as follows: (i) a large magnetization current is first generated on the surface of the HTS bulks after rapid field-cooling (FC) magnetization; (ii) the magnetization current then relaxes inwards step-by-step obeying the critical state model; (iii) after tens of backward iterations the magnetization current reaches a steady state. The simulation results show excellent agreement with the H -formulation method for both the electromagnetic and electromagnetic-mechanical coupled analyses, but with significantly faster computation speed. The simulation results using the backward computation method are further validated by the recent experimental results of a five-period GdβBaβCuβO (GdBCO) bulk undulator. Solving the finite element analysis (FEA) model with 1.8 million degrees of freedom (DOFs), the backward computation method takes less than 1.4 h, an order of magnitude or higher faster than other state-of-the-art numerical methods. Finally, the models are used to investigate the influence of the mechanical stress on the distribution of the critical state magnetization current and the undulator field along the central axis
Composite structural motifs of binding sites for delineating biological functions of proteins
Most biological processes are described as a series of interactions between
proteins and other molecules, and interactions are in turn described in terms
of atomic structures. To annotate protein functions as sets of interaction
states at atomic resolution, and thereby to better understand the relation
between protein interactions and biological functions, we conducted exhaustive
all-against-all atomic structure comparisons of all known binding sites for
ligands including small molecules, proteins and nucleic acids, and identified
recurring elementary motifs. By integrating the elementary motifs associated
with each subunit, we defined composite motifs which represent
context-dependent combinations of elementary motifs. It is demonstrated that
function similarity can be better inferred from composite motif similarity
compared to the similarity of protein sequences or of individual binding sites.
By integrating the composite motifs associated with each protein function, we
define meta-composite motifs each of which is regarded as a time-independent
diagrammatic representation of a biological process. It is shown that
meta-composite motifs provide richer annotations of biological processes than
sequence clusters. The present results serve as a basis for bridging atomic
structures to higher-order biological phenomena by classification and
integration of binding site structures.Comment: 34 pages, 7 figure
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Inverse analysis of critical current density in a bulk high-temperature superconducting undulator
In order to optimise the design of undulators using high-temperature superconductor (HTS) bulks we have developed a method to estimate the critical current density (Jc) of each bulk from the overall measured magnetic field of an undulator. The vertical magnetic field was measured along the electron-beam axis in a HTS bulk-based undulator consisting of twenty Gd-Ba-Cu-O (GdBCO) bulks inserted in a 12-T solenoid. The Jc values of the bulks were estimated by an inverse analysis approach in which the magnetic field was calculated by the forward simulation of the shielding currents in each HTS bulk with a given Jc. Subsequently the Jc values were iteratively updated using the pre-calculated response matrix of the undulator magnetic field to Jc. We demonstrate that it is possible to determine the Jc of each HTS bulk with sufficient accuracy for practical application within around 10 iterations. The pre-calculated response matrix, created in advance, enables the inverse analysis to be performed within a practically short time, on the order of several hours. The measurement error, which destroys the uniqueness of the solution, was investigated and the points to be noted for future magnetic field measurements were clarified. The results show that this inverse-analysis method allows the estimation of the Jc of each bulk comprising an HTS bulk undulator.CHART (Swiss Accelerator Research and Technology Collaboration);
EPSRC Early Career Fellowship, EP/P020313/
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