Results and Discussion
The Tanimoto coefficients between histamine and other ligand molecules are shown in Table 2. Typically, a Tanimoto coefficient > 0.85 is considered highly similar, and a coefficient > 0.75 is considered similar for the purpose of clustering molecules that may have similar biological activity profiles [15]. The highest Tanimoto coefficient among agonists was 0.45 (imetit), and this is not high enough to be considered a molecule that has potential agonist efficacy. Moreover, the lowest value of Tanimoto coefficient among agonists was 0.08 (dimaprit and SKF91488) and is also a lower value as an antagonist. It seems that there is no related pattern between Tanimoto coefficients and the functional types of molecules in the case of histamine receptor agonists or antagonists.
To search for a novel characteristic for the classification of histamine receptor ligands, a kind of molecular calculation using agglomerative hierarchical clustering was adopted in this work. The result of the hierarchical clustering of the similarity matrix from CIMVF is shown in Fig. 2. As shown in the figure, eight agonists were located nearby (the part in the dotted circle), except impromidine, and all antagonists were clustered close to each other in the radial tree. We can tell the regional difference between agonists and antagonists in the tree and also find that the information from the molecular vibrational frequency may play a role in the classification of agonists/antagonists for histamine receptor as a possible molecular descriptor. For these methods, clustering with CIMVF shows the more proper result in the case of histamine receptor ligands. With a more concentrated study on the relationship between the molecular vibrational frequency and pharmacological function of a ligand, the vibrational spectrum of a molecule may shed light on the field of ligand-receptor interaction mechanisms.