INTEREST OF CLUSTER SIGNIFICANCE ANALYSIS IN STRUCTURE-AFFINITY RELATIONSHIPS FOR NONXANTHINE HETEROCYCLIC ANTAGONISTS OF ADENOSINE

In order to define some predictive rules for the discrimination of ade nosine antagonists by their A, receptor affinity, we performed a syste matic QSAR analysis. As no significant descriptors of affinity were fo und, we then proposed to introduce a calculated enthalpy or entropy ch ange for the interaction as a first approximation of the affinity desc riptors. Since the structural details of the common receptor binding s ite remain to be determined, we utilized an indirect strategy involvin g the simulation of amino acid residues that are thought to interact w ith the ligand. Estimating enthalpic and entropic components by means of a semi-empirical quantum mechanical AM 1 force calculation, we foun d a significant clustering of enthalpy change values. This method prov ides a good descriptor of interaction and also a simple tool for testi ng hypotheses on the nature of putative binding sites.