Exploration of Ultralarge Compound Collections for Drug Discovery.

Designing new medicines more cheaply and quickly is tightly linked to the quest of exploring chemical space more widely and efficiently. Chemical space is monumentally large, but recent advances in computer software and hardware have enabled researchers to navigate virtual chemical spaces containing billions of chemical structures. This review specifically concerns collections of many millions or even billions of enumerated chemical structures as well as even larger chemical spaces that are not fully enumerated. We present examples of chemical libraries and spaces and the means used to construct them, and we discuss new technologies for searching huge libraries and for searching combinatorially in chemical space. We also cover space navigation techniques and consider new approaches to de novo drug design and the impact of the "autonomous laboratory" on synthesis of designed compounds. Finally, we summarize some other challenges and opportunities for the future.

A CADD-alog of strategies in pharma.

A special issue on computer-aided drug design (CADD) strategies in pharma discusses how CADD groups in different environments work. Perspectives were collected from authors in 11 organizations: four big pharmaceutical companies, one major biotechnology company, one smaller biotech, one private pharmaceutical company, two contract research organizations (CROs), one university, and one that spans the breadth of big pharmaceutical companies and one smaller biotech.

A Short Review of Chemical Reaction Database Systems, Computer-Aided Synthesis Design, Reaction Prediction and Synthetic Feasibility.

This article is the text for a pedagogical lecture to be given at the Strasbourg Summer School in Chemoinformatics in June 2104. It covers a very wide range of reaction topics including structure and reaction representation, reaction centers, atom-to-atom mapping, reaction retrieval systems, computer-aided synthesis design, retrosynthesis, reaction prediction and synthetic feasibility. In the time available the coverage of each topic can only be cursory; the main usefulness of this article to the research community is the extensive bibliography.

Some Trends in Chem(o)informatics.

This introductory chapter gives a brief overview of the history of cheminformatics, and then summarizes some recent trends in computing, cultures, open systems, chemical structure representation, docking, de novo design, fragment-based drug design, molecular similarity, quantitative structure-activity relationships (QSAR), metabolite prediction, the use of phamacophores in drug discovery, data reduction and visualization, and text mining. The aim is to set the scene for the more detailed exposition of these topics in the later chapters.

Tautomerism in chemical information management systems.

Tautomerism has an impact on many of the processes in chemical information management systems including novelty checking during registration into chemical structure databases; storage of structures; exact and substructure searching in chemical structure databases; and depiction of structures retrieved by a search. The approaches taken by 27 different software vendors and database producers are compared. It is hoped that this comparison will act as a discussion document that could ultimately improve databases and software for researchers in the future.

Evaluation of an experimental chemistry preprint server.

A preprint is a research article made publicly available prior to formal publication. A preprint server is a freely available archive and distribution medium for preprints, allowing rapid dissemination and use of multimedia and supporting files. Electronic eprints have been widely adopted in certain fields (notably high energy physics), but, until recently, the preprint concept has not been received with enthusiasm by most chemists. Despite the fact that preprints have the advantage of rapid publication, chemists have been reluctant to produce them because they could be viewed as "unallowable" for research assessment or tenure exercises or for publication in certain prestigious journals. In theory, preprints, together with version control and online discussion, could be a useful compromise: rapid prepublication followed by open peer review, before publication in a traditional journal. This paper constitutes a preliminary evaluation of a Chemistry Preprint Server in its second year of operation and summarizes the lessons that can be learned from the experiment to date.