Pirard, Bernard (2011) The quest for novel chemical matter. Expert Opinion in Drug Discovery, 6 (3). pp. 226-231. ISSN 1746-0441

Abstract

Importance to the field: Identifying novel chemical matter is the focus of many drug discovery efforts. Computer-based de novo design of drug-like molecules has emerged as a valuable approach to identify novel chemical matter. De novo design aims to build in silico an entire molecule “from scratch”. It is complementary to other approaches such as high throughput screening, fragment-based screening or virtual screening.
Areas covered in this review: Herein we discuss recent research efforts that aim to build in silico more chemically accessible molecules, to sample more efficiently the chemical space and to rank the proposed molecules. De novo design algorithms developed between 2008 and 2010 are also reviewed. We also discuss the issue of validation. Finally, we highlight some recent successful applications of de novo design to drug discovery projects.
What the reader will gain: The reader is provided with an overview of the recent methodological developments and applications of de novo design. As a result, the reader will gain valuable insights into the challenges, the limitations and the opportunities of de novo design.
Take home message: Research has addressed some of the limitations of the early versions of de novo design softwares, in particular the lack of synthetic accessibility of the proposed molecules. The lack of accurate function to score molecules generated within a binding site remains a major limitation. Large-scale validation studies are still missing. Despite these limitations, de novo design is a valuable approach to generate either chemical starting points or ideas.

Item Type:	Article
Keywords:	de novo design, hit finding, fragment space, natural computing, scoring, multi-objective scoring
Date Deposited:	13 Oct 2015 13:15
Last Modified:	13 Oct 2015 13:15
URI:	https://oak.novartis.com/id/eprint/3799