Set-up and screening of a fragment library targeting the 14-3-3 protein interface

The modeling of protein assemblies on the atomic level remains a central issue in structural biology, as protein interactions play a key role in numerous cellular processes. This problem is traditionally addressed using docking tools, where the quality of the models that are produced is based on their similarity to a single reference experimental structure. However, this approach using a static reference does not take into account the dynamic quality of the protein interface. Here, we used all-atom classical Molecular Dynamics simulations to investigate the stability of the interface for three complexes that previously served as targets in the CAPRI competition, and for each one of these targets, ten models distributed over the High, Medium and Acceptable categories. To assess the quality of these models from a dynamic perspective, we set up new criteria which take into account the stability of the reference protein interface. We show that, when the protein interfaces are allowed to evolve along time, the original ranking based on the static CAPRI criteria no longer holds as over 50% of the docking models undergo a category change (either toward a better or a lower group) when reassessing their quality using dynamic information.

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PHYSICOCHEMICAL PROPERTIES OF S-ZONE AND BASE PROTEINS IN GLUTEN

Canadian Journal of Biochemistry ◽

10.1139/o66-108 ◽

1966 ◽

Vol 44 (6) ◽

pp. 917-925 ◽

Cited By ~ 1

Author(s):

Yang H. Oh ◽

Benjamin E. Sanders ◽

Charles W. Gehrke

Keyword(s):

Amino Acid ◽

Physicochemical Properties ◽

Protein Interactions ◽

Wheat Gluten ◽

Amino Acid Content ◽

Low Molecular Weight ◽

Protein Protein Interactions ◽

Contributing Factors ◽

Protein Molecules ◽

Stable Structures

Some of the physicochemical properties (solubility, viscosity, sedimentation) and the amino acid composition of the isolated S-zone and base proteins from soft-wheat gluten were studied. The S-zone proteins are homogeneous in size, of low molecular weight (about 20,000), and high intrinsic viscosity in buffer of pH 3,5, having stable structures whose unique solubility properties are related to their atypical amino acid content. The base protein molecules exist in a more folded conformation, having the properties of globular protein molecules. The protein–protein interactions, aggregation, and unfolding conformation of S-zone proteins are major contributing factors at neutral pH to the rheological properties of wheat flour, such as viscosity, elasticity, and cohesiveness.

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Protein-protein interactions in contact activation of blood coagulation. Characterization of fluorescein-labeled human high molecular weight kininogen-light chain as a probe.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)43773-2 ◽

1983 ◽

Vol 258 (24) ◽

pp. 15079-15086 ◽

Cited By ~ 3

Author(s):

P E Bock ◽

J D Shore

Keyword(s):

Molecular Weight ◽

Blood Coagulation ◽

High Molecular Weight ◽

Protein Interactions ◽

Light Chain ◽

High Molecular Weight Kininogen ◽

Protein Protein Interactions ◽

Contact Activation

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Determination of the molecular weight of proteins in heterogeneous mixtures: Use of an air-driven ultracentrifuge for the analysis of protein-protein interactions

Archives of Biochemistry and Biophysics ◽

10.1016/0003-9861(79)90345-x ◽

1979 ◽

Vol 195 (1) ◽

pp. 235-242 ◽

Cited By ~ 16

Author(s):

R.G. Clarke ◽

G.J. Howlett

Keyword(s):

Molecular Weight ◽

Protein Interactions ◽

Protein Protein Interactions

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Differences of Present Recommendations and Guidelines for Generic Low-Molecular-Weight Heparins: Is There Room for Harmonization

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029610392216 ◽

2011 ◽

Vol 17 (6) ◽

pp. E158-E164 ◽

Cited By ~ 5

Author(s):

Job Harenberg

Keyword(s):

Molecular Weight ◽

Patent Protection ◽

European Medicines Agency ◽

Low Molecular Weight ◽

Low Molecular Weight Heparins ◽

The North ◽

Scientific Organizations ◽

Set Up ◽

Medical Indications

Based on the results of large clinical trials, several low-molecular-weight heparins (LMWHs) have been approved for prophylaxis and the treatment of venous and arterial thromboembolism. As a result of expiration or pending expiration of patent protection of the originator LMWHs, the first generic LMWH enoxaparin has been approved by the Food and Drug Administration for clinical use in all medical indications. The European Medicines Agency has set up guidelines for the production of generic LMWHs. The International Society of Thrombosis, the North American Thrombosis Forum and other scientific organizations raised concerns regarding the safety of generic LMWHs due to economic reasons. These organizations have published statements for the production of generic LMWHs to ensure the quality of the products and the safety for patients. Ideally, the differences between the actual recommendations and guidelines for the production of generic version of LMWHs should be harmonized.

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