| 摘要 |
<p>This invention provides an improved format for pharmacophore fingerprints as well as improved methods of generating and using fingerprints. A specific embodiment provides a structure-activity relationship derived with the aid of pharmacophore fingerprints. A pharmacophore fingerprint for a chemical compound may specify a collection of individual pharmacophores that match the structure of the compound. Preferably, the fingerprint includes distinct pharmacophores that match distinct energetically favorable conformations. Some pharmacophores may match a first conformation but not a second conformation. Other pharmacophores may match the second conformation but not the first. Yet, the two conformations may each make significant contributions to the compound's activity. So the fingerprint should identify pharmacophores matching any appropriate conformation. The present invention also provides apparatus and methods for identifying, representing and productively using high activity regions of chemical space. Many representations of chemical space have been used and may be envisioned. In a preferred embodiment of this invention, at least two representations provide valuable information. A first representation has many dimensions defined by a pharmacophore basis set and one or more additional dimensions representing defined chemical activity (e.g., pharmacological activity). A second representation may be one of reduced dimensionality, where the coordinates can be derived from the first representation by a suitable mathematical technique such as, for example, the principle components produced by Principle Component Analysis using pharmacophore fingerprint/activity data for a collection of compounds.</p> |
