Fingerprints protein similarity

Sahm N, Holliday J, Willett P. (2003) Combination of Fingerprint-Based Similarity Coefficients Using Data Fusion. /. Chem. Inf. Comp. Set. 43 435-442. Schuffenhauer A, Floersheim P, Acklin P, Jacoby E. (2003) Similarity Metrics for Ligands Reflecting the Similarity of the Target Proteins. J. Chem. Inf. Comp. Set. 43 391-405. 

Because the interaction fingerprint represents the binding mode of a ligand to a target protein, similar fingerprints imply that the corresponding ligands make similar interactions with the protein. 

Liu, J., Yang, L., Li, Y, Pan, D. and Hopfinger, A.J. (2006) Constructing plasma protein binding model based on a combination of cluster analysis and 4D-fingerprint molecular similarity analyses. Bioorg. Med. Chem., 14, 611-621. 

This is the concept of the Multildent tool [50, http //www.expasy.org/tools/ multiident/)]. Multildent first generates a list of best-matching proteins by amino acid composition, whose sequences are then digested theoretically and the resulting peptide masses matched against the experimentally obtained peptide mass fingerprint of the unknown protein. Similarly to... 

The characteristic derivative-shaped feature at g 1.94 first observed in mitochondrial membranes has long been considered as the sole EPR fingerprint of iron-sulfur centers. The EPR spectrum exhibited by [4Fe-4S] centers generally reflects a ground state with S = I and is characterized by g values and a spectral shape similar to those displayed by [2Fe-2S] centers (Fig. 6c). Proteins containing [4Fe-4S] centers, which are sometimes called HIPIP, essentially act as electron carriers in the photoinduced cyclic electron transfer of purple bacteria (106), although they have also been discovered in nonphotosynthetic bacteria (107). Their EPR spectrum exhibits an axial shape that varies little from one protein to another with g// 2.11-2.14 and gi 2.03-2.04 (106-108), plus extra features indicative of some heterogeneous characteristics (Pig. 6d). 

The i-poly(3HB) depolymerase of R. rubrum is the only i-poly(3HB) depolymerase that has been purified [174]. The enzyme consists of one polypeptide of 30-32 kDa and has a pH and temperature optimum of pH 9 and 55 °C, respectively. A specific activity of 4 mmol released 3-hydroxybutyrate/min x mg protein was determined (at 45 °C). The purified enzyme was inactive with denatured poly(3HB) and had no lipase-, protease-, or esterase activity with p-nitro-phenyl fatty acid esters (2-8 carbon atoms). Native poly(3HO) granules were not hydrolyzed by i-poly(3HB) depolymerase, indicating a high substrate specificity similar to extracellular poly(3HB) depolymerases. Recently, the DNA sequence of the i-poly(3HB) depolymerase of R. eutropha was published (AB07612). Surprisingly, the DNA-deduced amino acid sequence (47.3 kDa) did not contain a lipase box fingerprint. A more detailed investigation of the structure and function of bacterial i-poly(HA) depolymerases will be necessary in future. 

Once the protein interaction pattern is translated from Cartesian coordinates into distances from the reactive center of the enzyme and the structure of the ligand has been described with similar fingerprints, both sets of descriptors can be compared [25]. The hydrophobic complementarity, the complementarity of charges and H-bonds for the protein and the substrates are all computed using Carbo similarity indices [26]. The prediction of the site of metabolism (either in CYP or in UGT) is based on the hypothesis that the distance between the reactive center on the protein (iron atom in the heme group or the phosphorous atom in UDP) and the interaction points in the protein cavity (GRID-MIF) should correlate to the distance between the reactive center of the molecule (i.e. positions of hydrogen atoms and heteroatoms) and the position of the different atom types in the molecule [27]. 

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