Tertiary protein structure improvements

W. F. van Gunsteren, R. Boelens, R. Kaptein, R. M. Scheek, and E. R. P. Zuiderweg, in Molecular Dynamics and Protein Structure, J. Hermans, Ed., Polycrystal Book Service, Western Springs, Illinois, 1985, pp. 92-99. An Improved Restrained Molecular Dynamics Technique to Obtain Protein Tertiary Structure from Nuclear Magnetic Resonance Data. 

Sweet (69), Levin et al. (70) and Nishikawa and Ooi (71) all converged on the notion to utilize consensus secondary structures of oligopeptides in the data bank of known three-D protein structures. A window is defined (7 to 12 residues). Each such span in the sequence to be predicted is judged as homologous to several spans in the known tertiary stuctures. The consensus structure of the positions in the known spans allows a prediction for the unknown span. Moving along the sequence one residue at a time, the window process is repeated and the preferred secondary structure at a particular position taken as the prediction. Generally, there is little improvement over older methods. 

Improvements in the ability to predict tertiary structure will allow these techniques to assist in the rapid determination of protein structures. Such tools are necessary if structural genomics, which is designed to determine the tertiary structure of all proteins [220-222], is to make major progress. By suggesting proteins of novel fold and/or function, tertiary structure prediction can be used to prioritize the selection of proteins whose structure will determined by experiment. It will also assist in the rapid determination of the structure of... 

The extrusion process frequently results in realignment of disulfide bonds and breakage of intramolecular bonds. Disulfide bonds stabilize the tertiary structure of protein and may limit protein imfolding during extrusion (Taylor et al., 2006). Flow and melt characteristics were improved when other proteins were extruded with disulfide reducing agents (Areas, 1992), which indicates that disulfide bonds adversely affect... 

In an alternative approach the site-selective functionalization reaction has been used to incorporate a galactose derivative into a folded foux-hehx bundle protein and the effect of glycosylation on the structure of the folded protein has been identified [65]. The unfunctionalized designed four-helix bundle did not have a well-defined tertiary structure but the introduction of the sugar improved the helical content and reduced the rate of conformational exchange. Glycosylation may therefore play a role in the maturation of poorly folded proteins. 

Bioassays may be the most important assays since they are often the only available tools for determining the correct tertiary structure of complex protein products and the activity of even more complex biotechnology products. Bioassays are also the most problematic assays, and the variability may be 50% for animal-based bioassays. New developments in sensor technologies may improve both the speed and accuracy of bioassays [9]. The development of hematopoietic stem cells for in vitro assays has the potential to increase both the accuracy and the speed of bioassays [10]. 

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