31 research outputs found
Tools and data services registry: a community effort to document bioinformatics resources.
Life sciences are yielding huge data sets that underpin scientific discoveries fundamental to improvement in human health, agriculture and the environment. In support of these discoveries, a plethora of databases and tools are deployed, in technically complex and diverse implementations, across a spectrum of scientific disciplines. The corpus of documentation of these resources is fragmented across the Web, with much redundancy, and has lacked a common standard of information. The outcome is that scientists must often struggle to find, understand, compare and use the best resources for the task at hand.Here we present a community-driven curation effort, supported by ELIXIR-the European infrastructure for biological information-that aspires to a comprehensive and consistent registry of information about bioinformatics resources. The sustainable upkeep of this Tools and Data Services Registry is assured by a curation effort driven by and tailored to local needs, and shared amongst a network of engaged partners.As of November 2015, the registry includes 1785 resources, with depositions from 126 individual registrations including 52 institutional providers and 74 individuals. With community support, the registry can become a standard for dissemination of information about bioinformatics resources: we welcome everyone to join us in this common endeavour. The registry is freely available at https://bio.tools
Examination of the adhesion of plasma sprayed coatings
17.00; Translated from Czech (Zvaranie 1986 v. 35 (6) p. 181-184)SIGLEAvailable from British Library Document Supply Centre- DSC:9023.19(VR--3197)T / BLDSC - British Library Document Supply CentreGBUnited Kingdo
TransportTools: a library for high-throughput analyses of internal voids in biomolecules and ligand transport through them
Information regarding pathways through voids in biomolecules and their roles in ligand transport is critical to our understanding of the function of many biomolecules. Recently, the advent of high-throughput molecular dynamics simulations has enabled the study of these pathways, and of rare transport events. However, the scale and intricacy of the data produced requires dedicated tools in order to conduct analyses efficiently and without excessive demand on users. To fill this gap, we developed the TransportTools, which allows the investigation of pathways and their utilization across large, simulated datasets. TransportTools also facilitates the development of custom-made analyses
Engineering a de Novo Transport Tunnel
Transport of ligands between buried
active sites and bulk solvent
is a key step in the catalytic cycle of many enzymes. The absence
of evolutionary optimized transport tunnels is an important barrier
limiting the efficiency of biocatalysts prepared by computational
design. Creating a structurally defined and functional “hole”
into the protein represents an engineering challenge. Here we describe
the computational design and directed evolution of a de novo transport
tunnel in haloalkane dehalogenase. Mutants with a blocked native tunnel
and newly opened auxiliary tunnel in a distinct part of the structure
showed dramatically modified properties. The mutants with blocked
tunnels acquired specificity never observed with native family members:
up to 32 times increased substrate inhibition and 17 times reduced
catalytic rates. Opening of the auxiliary tunnel resulted in specificity
and substrate inhibition similar to those of the native enzyme and
the most proficient haloalkane dehalogenase reported to date (<i>k</i><sub>cat</sub> = 57 s<sup>–1</sup> with 1,2-dibromoethane
at 37 °C and pH 8.6). Crystallographic analysis and molecular
dynamics simulations confirmed the successful introduction of a structurally
defined and functional transport tunnel. Our study demonstrates that,
whereas we can open the transport tunnels with reasonable proficiency,
we cannot accurately predict the effects of such change on the catalytic
properties. We propose that one way to increase efficiency of an enzyme
is the direct its substrates and products into spatially distinct
tunnels. The results clearly show the benefits of enzymes with de
novo transport tunnels, and we anticipate that this engineering strategy
will facilitate the creation of a wide range of useful biocatalysts
Structural and Functional Analysis of Novel Haloalkane Dehalogenase with Two Halide Binding Sites
The crystal structure of the novel haloalkane dehalogenase DbeA fromBradyrhizobium elkaniiUSDA94 revealed the presence of two chloride ions buried in the protein interior. The first halide-binding site is involved in substrate binding and is present in all structurally characterized haloalkane dehalogenases. The second halide-binding site is unique to DbeA. To elucidate the role of the second halide-binding site in enzyme functionality, a two-point mutant lacking this site was constructed and characterized. These substitutions resulted in a shift in the substrate-specificity class and were accompanied by a decrease in enzyme activity, stability and the elimination of substrate inhibition. The changes in enzyme catalytic activity were attributed to deceleration of the rate-limiting hydrolytic step mediated by the lower basicity of the catalytic histidine.</jats:p
Selected characteristics of powders for plasma thermal spraying
22.00; Translated from Czech. (Zvaranie 1987 (1) p. 10-12)Available from British Library Document Supply Centre- DSC:9022.0602(BISI-NF-Trans--347)T / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo