PMC:4331677 / 26760-29766
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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4331677","sourcedb":"PMC","sourceid":"4331677","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4331677","text":"Fragment interaction network analysis\nIn this section, we first give a brief overview of fragment interaction matrix. Then we investigate the underlying chemical mechanisms of fragments interactions.\nAn obvious feature of the fragment interaction matrix (Figure 5A) is that the values can be positive and negative, which means some fragment interactions are in favor of binding, and others not. Another obvious feature is that most of the values are close to zeros, which means the connections between site and ligand fragments are sparse. The sparse connection implies a site fragment only could recognize a small number of ligand fragments, which could reflect the specificity during the target-ligand binding procedure. Although there are 148653 (199 ∗ 747) elements in the matrix, only those whose value is larger than 0.1 are viewed as significant (the average standard error is 0.1). As a result, there are 9243 significant interactions in the network. During the significant interactions, the interaction values larger than 0.25 (top 20%) are regarded as import. Figure 5B shows the import fragment interactions.\nFigure 5 Interaction network analysis. A) An overview of feature interaction network. The horizontal ordinate and longitudinal coordinates are ligand features and target features respectively. B) The import interaction network (a subnetwork of fragment interaction network). C) The top twenty interactions. The interactions can reflect the chemical interaction. According to the hypothesis, the feature interactions reflect the chemical interaction, as a result, it is necessary to investigate whether the feature interactions response the hypothesis. Since the number of interactions is large, we only analyze the top twenty interactions (Figure 5C), the others could be analyzed similarly. In Figure 5C, the first letter of site fragment is the center amino acid of the trimer cluster, and the letters in the parenthesis represent the subordinate amino acids. The smarts (a kind of molecular patterns) represent ligand fragments. The Figure 5C suggest that the feature interactions reflect the chemical interaction well, which in consistent with the hypothesis. For example, the major amino acid of site fragment 147 (TF147) is Aspartic (short for D), which could interact with ligand fragment 92 (LF92, containing keto group) through hydrogen bond, if the distance and orientation are appropriate. In some situations, the major amino acid of a target feature could not form significant interaction with ligand feature, but the subsidiary amino acid could. For example, the major amino acid of site fragment 57 (TF57) is isoleucine (short for I), which is a hydrophobic amino acid. Isoleucine could not interact with ligand fragment 44 (LF44), which contains amino group. However, the subsidiary amino acid of site fragment 57, such as threonine (short for T) and arginine (short for R) can form hydrogen bond with ligand fragment 44, if the distance and orientation are appropriate.","divisions":[{"label":"title","span":{"begin":0,"end":37}},{"label":"p","span":{"begin":38,"end":199}},{"label":"p","span":{"begin":200,"end":1119}},{"label":"figure","span":{"begin":1120,"end":1482}},{"label":"label","span":{"begin":1120,"end":1128}},{"label":"caption","span":{"begin":1130,"end":1482}},{"label":"p","span":{"begin":1130,"end":1482}}],"tracks":[]}