| 摘要 |
<p>The method to rapidly retrieve potentially active analogs of a lead compound according to the invention generates and screens from a large database of 3D multiconformational fingerprints of chemically feasible combinatorial products mainly by linking radicals temporarily to a bulky spacekeeper group, registering 3D models of the radicals in a combinatorial ghost database, for any molecular structure that is accessible within the ghost database, detecting any atom that displays physical property features of the pharmacophoric type; for the pairs of pharmacophores detected in each molecular structure, calculating all the distances between the involved atoms in every conformation of this molecule and creating a distance distribution density; generating a conformational fingerprint vector that contains all the distance distribution densities of the pairs of pharmacophores; defining a scoring function for each molecular fingerprint according for the relative importance of the pharmacophoric features; generating the fingerprints for the lead compound and comparing these fingerprints to each fingerprint of the potential library according to the above scoring function as maximized for the lead, and retrieving the molecules of the potential library for which the scoring function gives score values less than a specified threshold.</p> |
