Chapter category: Drug Design
Analysis of Chemical Space
Adaptive Systems in Drug Design
Edited by: Gisbert SchneiderISBN: 1-58706-059-0
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Chapter authors:
Gisbert Schneider
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A main goal of virtual screening is to select activity-enriched sets of molecules — or single molecules exhibiting desired activity—from the space of all synthetically accessible structures. Currently the most advanced HTS techniques allow for testing of ~105 compounds per day, and a typical corporate screening library contains several hundred thousand samples. Although these facts alone represent a technological revolution, the turnover numbers still are extremely small compared with the total size of chemical space.1 As a consequence, even ultra HTS combined with fast, parallel combinatorial chemistry can only be successful if a reasonable pre-selection of molecules (or molecular building blocks) for screening is done. Otherwise this approach will more or less represent a random search with a very small probability of success. While HTS and ultraHTS have made significant progress in recent years, we should bear in mind that it will be very costly to screen a million of compounds for activity in all the new receptor assays (estimated $0.1 to $10 per compound per screen). Even if a company has these resources, it is rare that they have access to a diverse one-million-compound screening library. Thus it can be advantageous to integrate VS tools into the drug discovery process to find leads with novel scaffolds by either starting from competitor compounds described in the literature and/or from a proprietary, existing scaffold. Once a reliable VS process has been defined it can save resources and limit experimental efforts by suggesting defined sets of molecules.
Additional chapters from this book:
Analysis of Chemical Space
Gisbert Schneider
A main goal of virtual screening is to select activity-enriched sets of molecules — or single molecules exhibiting desired activity—from the space of all synthetically accessible ...
Evolutionary De Novo Design
Gisbert Schneider
"GAs have been shown to be capable of describing extremely complex bahaviour in a range of application domains, including those of molecular recognition and design." (P. Willett)
Prediction of Drug-Like Properties
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Historically, computer-aided molecular design (CAMD) has focused on lead identification and lead optimization, and many innovative strategies have been developed that assist in improving th...
Modeling Structure-Activity Relationships
Gisbert Schneider
Traditionally, the design of novel drugs has essentially been a trial-and-error process despite the tremendous efforts devoted to it by pharmaceutical and academic research groups. It is es...
A Conceptual Framework
Gisbert Schneider
"It is no longer just sufficient to synthesise and test; experiments are played out in silico with prediction, classification, and visualisation being the necessary tools of medicin...
