Modeling of substrate and inhibitor binding to phospholipase A2.

Molecular graphics and molecular mechanics techniques have been used to study the mode of ligand binding and mechanism of action of the enzyme phospholipase A2. A substrate-enzyme complex was constructed based on the crystal structure of the apoenzyme. The complex was minimized to relieve initial strain, and the structural and energetic features of the resultant complex analyzed in detail, at the molecular and residue level. The minimized complex was then used as a basis for examining the action of the enzyme on modified substrates, binding of inhibitors to the enzyme, and possible reaction intermediate complexes. The model is compatible with the suggested mechanism of hydrolysis and with experimental data about stereoselectivity, efficiency of hydrolysis of modified substrates, and inhibitor potency. In conclusion, the model can be used as a tool in evaluating new ligands as possible substrates and in the rational design of inhibitors, for the therapeutic treatment of diseases such as rheumatoid arthritis, atherosclerosis, and asthma.     

Iris: Interactive all‐in‐one graphical validation of 3D protein model iterations

Iris validation is a Python package created to represent comprehensive per‐residue validation metrics for entire protein chains in a compact, readable and interactive view. These metrics can either be calculated by Iris, or by a third‐party program such as MolProbity. We show that those parts of a protein model requiring attention may generate ripples across the metrics on the diagram, immediately catching the modeler's attention. Iris can run as a standalone tool, or be plugged into existing structural biology software to display per‐chain model quality at a glance, with a particular emphasis on evaluating incremental changes resulting from the iterative nature of model building and refinement. Finally, the integration of Iris into the CCP4i2 graphical user interface is provided as a showcase of its pluggable design.     

GPU-accelerated molecular dynamics simulation of solid covalent crystals

Graphics processing unit (GPU) is becoming a powerful computational tool in science and engineering. In this paper, different from previous molecular dynamics (MD) simulation with pair potentials and many-body potentials, two MD simulation algorithms implemented on a single GPU are presented to describe a special category of many-body potentials – bond order potentials used frequently in solid covalent materials, such as the Tersoff potentials for silicon crystals. The simulation results reveal that the performance of GPU implementations is apparently superior to their CPU counterpart. Furthermore, the proposed algorithms are generalised, transferable and scalable, and can be extended to the simulations with general many-body interactions such as Stillinger–Weber potential and so on.     

Ecology and the War on Hunger

This interdisciplinary activity promotes science, technology, and language arts and is well suited for upper elementary grade students. In the activity, students' research about a teacher-assigned weather phenomenon facilitates their study of the weather. When they have completed their research, students word process a paper summarizing their findings and generate graphical representations of a weather phenomenon using Microsoft Paint software. The paper and the computer-generated graphical representation measure learning and provide insight into the level of student understanding that other assessment tools, such as quizzes, tests, and questioning techniques, do not provide.     

The tertiary structure of Aspergillus saitoi minor ribonuclease (Ms) predicted from the structure of RNase T1

Ribonuclease Ms from Aspergillus saitoi is a small acidic protein (11 714 Da) containing 106 amino acids of known sequence. Unlike other enzymes belonging to the RNase T₁ family this ribonuclease is base-unspecific. Using interactive computer graphics and energy minimisation we predicted the structure of RNase Ms on the basis of sequence homology to RNase T₁ of known structure. In this report the predicted structure of this protein is presented and characterised.     

X-ray and model-building studies on the specificity of the active site of proteinase K

Proteinase K, the extracellular serine endopeptidase (E.C. 3.4.21.14) from the fungus Tritirachium album limber, is homologous to the bacterial subtilisin proteases. The binding geometry of the synthetic inhibitor carbobenzoxy-Ala-Phechloromethyl Ketone to the active site of proteinase K was the first determined from a Fourier synthesis based on synchrotron X-ray diffraction data between 1.8 Å and 5.0 Å resolution. The protein inhibitor complexes was refined by restrained least-squares minimization with the data between 10.0 and 1.8 Å. The final R factor was 19.1% and the model contained 2,018 protein atoms, 28 inhibitors atoms, 125 water molecules, and two Ca²⁺ ions. The peptides portion of the inhibitor is bound to the active center of proteinase K by means of a three-stranded antiparallel pleated sheet, with the side chain of the phenylalanine located in the P1 site. Model building studies, with lysine replacing phenylalanine in the inhibitor, explain the relatively unspecific catalytic activity of the enzyme.     

High resolution positioning of intron ends on the nucleosomes

High resolution sequence-directed nucleosome mapping is applied to 36,000 sequences containing splice junctions, from five different species. As it has been also shown in previous studies, the junctions are found to be preferentially located within nucleosomes. Moreover, the orientation of guanine residues at the GT- and AG-ends of introns within the nucleosomes is such that the guanines are positioned nearest to the surface of histone octamers, 3 and 4 bases upstream from the local DNA pseudo-dyads passing through minor grooves oriented outwards. Since the guanine residues are the most vulnerable to spontaneous damage within the cell (primarily, depurination and oxidation) such positioning of the splice junctions minimizes the damage that is caused by free radicals and highly reactive metabolites.     

Program MULDER -- a tool for extracting torsion angles from NMR data

MULDER (Mostly UniversaL Dihedral angle ExtractoR) is a program for extraction of torsion angle information from NMR data. Currently, it can analyze two types of input data: The torsion angle data, where several ³J-coupling constants and/or interatomic distances are combined in order to reduce the torsion angle ambiguity arising from solving the isolated Karplus (or distance) equation, and the sugar pucker data, where the dynamics of five-membered sugar rings is evaluated by postprocessing the results calculated from ³J_(HH) coupling constants by program PSEUROT. Program MULDER can be used either as an alternative to r-MD programs in situations where only specific structural features are studied, or as a preparatory tool in connection with full r-MD structure calculation for extraction of unambiguous torsion angle restraints.     

GSDS: 基因结构显示系统

构建了一个用于绘制基因结构示意图的网站系统(http://gsds.cbi.pku.edu.cn/)。用户可提交核酸序列、NCBI核酸序列号或基因外显子位置信息, 得到基因结构示意图; 并可指定在基因结构图上标注某些特定区域。系统允许用户同时输入多个基因, 并指定输出次序和标注区域。结果可用位图和矢量图两种图形格式显示。点击位图格式结果, 可以查看相应序列。系统提供中英文两种用户界面。     

Semi-extended solution structure of human myeloma immunoglobulin D determined by constrained X-ray scattering

Human immunoglobulin D (IgD) occurs most abundantly as a membrane-bound antibody on the surface of mature B cells (mIgD). IgD possesses the longest hinge sequence of all the human antibody isotypes, with 64 residues connecting the Fab and Fc fragments. A novel rapid purification scheme of secreted IgD from the serum of an IgD myeloma patient using thiophilic (T-gel) and lectin affinity chromatography gave a stable, homogeneous IgD preparation. Synchrotron X-ray scattering and analytical ultracentrifugation of IgD identified the solution arrangement of its Fab and Fc fragments, and thereby its hinge structure. The Guinier X-ray radius of gyration R(G) of 6.9(+/-0.1)nm showed that IgD is more extended in solution than the immunoglobulin subclass IgA1 (R(G) of 6.1-6.2nm). Its distance distribution function P(r) showed a single peak at 4.7nm and a maximum dimension of 23nm. Velocity experiments gave a sedimentation coefficient of 6.3S, which is similar to that for IgA1 at 6.2S. The complete IgD structure was modelled using molecular dynamics to generate IgD hinge structures, to which homology models for the Fab and Fc fragments were connected. Good scattering curve fits were obtained with 18 semi-extended best fit IgD models that were filtered from 8500 trial models. These best-fit models showed that the IgD hinge does not correspond to an extended polypeptide structure. The averaged solution structure arrangement of the Fab and Fc fragments in IgD is principally T-shaped and flexible, with contribution from Y-shaped and inverted Y-shaped structures. Although the linear sequence of the IgD hinge is much longer, comparison with previous scattering modelling of IgA1 and IgA2(m)1 suggests that the hinge of IgA1 and IgD are more similar than might have been expected, Both possess flexible T-shaped solution structures, probably reflecting the presence of restraining O-linked sugars.