The atom assignment problem in automated de novo drug design. 1. Transferability of molecular fragment properties

This paper is the first of a series which examines the problems of atom assignment in automated de novo drug design. In subsequent papers, a combinatoric optimization method for fragment placement onto 3D molecular graphs is provided. Molecules are built from molecular graphs by placing fragments onto the graph. Here we examine the transferability of atomic residual charge, by fragment placement, with respect to the electrostatic potential. This transferability has been tested on 478 molecular structures extracted from the Cambridge Structural Database. The correlation found between the electrostatic potential computed from composite fragments and that computed for the whole molecule was encouraging, except for extended conjugated systems.