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PRO_LIGAND: an approach to de novo molecular design. 2. Design of novel molecules from molecular field analysis (MFA) models and pharmacophores.

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Waszkowycz B,Clark DE,Frenkel D,Li J,Murray CW,Robson B,Westhead DR

doi

10.1021/jm00049a019

subject

Has Abstract

pub_date

1994-11-11 00:00:00

pages

3994-4002

issue

23

eissn

0022-2623

issn

1520-4804

journal_volume

37

pub_type

杂志文章

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