Structural knowledge

Aptula AO, Cronin MTD. Prediction of hERG K blocking potency application of structural knowledge. SAR QSAR Environ Res 2004 15 399-411. 

By its very definition, the MaxEnt method is optimally suited to flexibly reconstruct distributions whose main features are well represented in the available data, that is either in the observations or in the prior structural knowledge. When this is the case, the missing structure can be reasonably approximated by a collection of randomly and independently distributed constituents (by missing structure here we mean all those structural details which are not completely defined by the prior knowledge). 

A considerable wealth of information is available on the general chemistry of these substances but precise structural knowledge is still lacking and a wide field of research awaits the activities of the chemist. This field not only covers carbohydrate and protein chemistry, but the area lying between the two, and it also borders on the lipid field. 

In the case of human amylin and Afi our understanding of the diversity in amyloid fibril architecture is the result of a recursive process, since the early morphological observations were followed by assessment of the assembly pathway which in turn yielded a better understanding of fibril polymorphism. However, this structural knowledge is secondary compared to the discovery of small oligomers, globular oligomers, and early protofibrils that appear to be extremely cytotoxic (Hartley etal., 1999 Lambert et al, 1998 Walsh et al, 1999). 

E. Klipp, W. Liebermeister, and C. Wierling, Inferring dynamic properties of biochemical reaction networks from structural knowledge. Gen. Inform. Ser. 15(1), 125 137 (2004). 

In the absence of accurate structural information, the analysis based on anisotropic diffusion as discussed above cannot be applied. The use of the isotropic overall model is still possible (see below) because it does not require any structural knowledge. However, the isotropic model has to be validated, i.e. the degree of the overall rotational anisotropy has to be determined prior to such an analysis. 

A large number of methods have been established to address the gathering structural information. Some are based on the biophysical properties of the studied molecules, others on their chemical composition. A most important final step is to properly relate the structural knowledge to the inferred functionality. Currently, X-ray crystallography is the predominant technique for 3D structure determination, owing to its now practical simplicity, ease, and high level of automation as compared to the formerly tedious and time... 

During the previous few years, the number of RNA crystal structures has increased in an exponential manner. This is mainly due to the fact that RNA is increasingly viewed as a predominant part of biological processes such as translation, ribozyme catalysis, and gene regulation (RNAi (Kamath et ah, 2003), riboswitches (Barrick et ah, 2004), and mRNA-protein interactions (Lescure et ah, 2002)), for which the gap in structural knowledge is still deep despite the determination of the crystal structure of the ribosome (Clemons et ah, 2001 Ban et ah, 2000 Yusupov et ah, 2001). 

There are a number of excellent sources of information on copper proteins notable among them is the three-volume series Copper Proteins and Copper Enzymes (Lontie, 1984). A review of the state of structural knowledge in 1985 (Adman, 1985) included only the small blue copper proteins. A brief review of extended X-ray absorption fine structure (EXAFS) work on some of these proteins appeared in 1987 (Hasnain and Garner, 1987). A number of new structures have been solved by X-ray diffraction, and the structures of azurin and plastocyanin have been extended to higher resolution. The new structures include two additional type I proteins (pseudoazurin and cucumber basic blue protein), the type III copper protein hemocyanin, and the multi-copper blue oxidase ascorbate oxidase. Results are now available on a copper-containing nitrite reductase and galactose oxidase. 

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