Solvent accessible surface area approximations for rapid and accurate protein structure prediction

The burial of hydrophobic amino acids in the protein core is a driving force in protein folding. The extent to which an amino acid interacts with the solvent and the protein core is naturally proportional to the surface area exposed to these environments. However, an accurate calculation of the solvent-accessible surface area (SASA), a geometric measure of this exposure, is numerically demanding as it is not pair-wise decomposable. Furthermore, it depends on a full-atom representation of the molecule. This manuscript introduces a series of four SASA approximations of increasing computational complexity and accuracy as well as knowledge-based environment free energy potentials based on these SASA approximations. Their ability to distinguish correctly from incorrectly folded protein models is assessed to balance speed and accuracy for protein structure prediction. We find the newly developed “Neighbor Vector” algorithm provides the most optimal balance of accurate yet rapid exposure measures

Interactions in solution and crystallization of Aspergillus flavus urate oxidase

International audienceInterparticle interactions of urate oxidase from Aspergillus flavus have been studied by small-angle X-ray scattering to determine crystallization conditions. This enzyme is a homotetramer with a total molecular weight of 128 kDa. It is a slightly basic protein (pI between 7.5 and 8). The interaction potentials have been studied as a function of the main thermodynamic and chemical parameters: temperature, protein concentration, pH, salt nature and concentration, addition of polyols. In 10 mM sodium carbonate at pH 10.5, the interactions are slightly repulsive and become less repulsive with a pH closer to pI. With the addition of carbonate, the protein loses its tetrameric structure for a dimeric one; with formate, the tetrameric structure remains stable. We also studied the effect of polyethylene glycols as it had been done with high molecular weight proteins. With the addition of PEG 8 K, the interactions became less repulsive and even turned attractive with the addition of both PEG 8 K and salt. Protein crystals of urate oxidase were observed in slightly repulsive conditions (second virial coefficient A(2), about +10(-5) mol ml g(-2) instead of -2 to -8 x 10(-4) mol ml g(-2) for low molecular weight proteins). (C) 2001 Elsevier Science B.V. All rights reserved

Crystallographic Studies with Xenon and Nitrous Oxide Provide Evidence for Protein-dependent Processes in the Mechanisms of General Anesthesia

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Crystallographic Studies with Xenon and Nitrous Oxide Provide Evidence for Protein-dependent Processes in the Mechanisms of General Anesthesia

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JDTic-based Radioligands for PET Imaging of Kappa Opioid Receptors: Design, Synthesis, Pharmacology, Molecular Modeling Studies, Radiolabelling with Carbon-11 or Fluorine-18, and in vivo Characterization

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