As is well known, opioid ligands are a large group of structurally diversified GPCR ligands, and their structure-activity relationships (SARs) are highly complicated. Why can so diverse structures bind to the same binding pockets of opioid receptors? Are there structural correlations among them? How would they behave at the binding sites, with respect to their binding conformations, affinities and selectivity, etc.? Can we build a unified pharmacophore model for all the ligands? All these are the central issues involved in the long history of opioid ligand studies, while to sole them will be highly valuable for the improvement of current opioid drugs or the discovery of new agents. Template alignment moldeing is an innovative approach developed recently in our modeling-based studies in order to tackle the above issues. By aligning and comparing the various structural features of ligands with a model template, this approach can help to reveal the structural patterns as well as the correlations among the various ligands. Even though still in testing and validating, this approach has appeared to be rather straight yet effective in interpretation of the SARs of various opioid ligands. With this presentation, we will report our latest progress in the template alignment modeling on the three types of opioid ligands. We will apply a recently constructed artificial template along with typical examples to illustrate how to understand the potential structural correlations as well as the associated SARs of many opioid ligands,

Template alignment modeling of the structure-activity relationships of opioid ligands

256th National Meeting (2018)

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