PRO_LIGAND: an approach to de novo molecular design. 2. Design of novel molecules from molecular field analysis (MFA) models and pharmacophores.
A computational approach for molecular design, PRO_LIGAND, has been developed within the PROMETHEUS molecular design and simulation system in order to provide a unified framework for the de novo generation of diverse molecules which are either similar or complementary to a specified target. In this instance, the target is a pharmacophore derived from a series of active structures either by a novel interpretation of molecular field analysis data or by a pharmacophore-mapping procedure based on clique detection. After a brief introduction to PRO_LIGAND, a detailed description is given of the two pharmacophore generation procedures and their abilities are demonstrated by the elucidation of pharmacophores for steroid binding and ACE inhibition, respectively. As a further indication of its efficacy in aiding the rational drug design process, PRO_LIGAND is then employed to build novel organic molecules to satisfy the physicochemical constraints implied by the pharmacophores.
Waszkowycz
B
B
Proteus Molecular Design Ltd., Macclesfield, Cheshire, United Kingdom.
Clark
D E
DE
Frenkel
D
D
Li
J
J
Murray
C W
CW
Robson
B
B
Westhead
D R
DR
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry; D015195:Drug Design; D008024:Ligands; D011944:Receptors, Androgen / Q000737:chemistry; D011980:Receptors, Progesterone / Q000737:chemistry; D012984:Software; D013256:Steroids / Q000737:chemistry; D013329:Structure-Activity Relationship
D000806:Angiotensin-Converting Enzyme Inhibitors; D008024:Ligands; D011944:Receptors, Androgen; D011980:Receptors, Progesterone; D013256:Steroids