Chapter category: Drug Design
A Conceptual Framework
Adaptive Systems in Drug Design
Edited by: Gisbert SchneiderISBN: 1-58706-059-0
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Chapter authors:
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 medicinal chemistry." (L. B. Kier)1
Pathological biochemical processes within a cell or an organism are usually caused by molecular interaction and recognition events. One major aim of drug discovery projects is to identify bioactive molecular structures that can be used to systematically interfere with such molecular processes and positively influence and eventually cure a disease. Both significant biological activity and specificity of action are important target functions for the molecular designer. In addition, one has to consider absorption, distribution, metabolic (ADME), and potential toxic properties during the drug development process to ensure that the drug candidate will have the desired pharmacokinetic and pharmacodynamic properties. Usually the initial "hit", i.e., a bioactive structure identified in a high-throughput screen (HTS) or any other biological test system, is turned into a "lead" structure. This often includes optimization/minimization towards ADME/Tox parameters. Further optimization is carried out as the compounds enters the next phases of drug discovery, namely lead optimization and development, nonclinical and finally clinical trials (Fig. 1). Only if all of the required conditions are met can the molecule become a trade drug. The target function in drug design clearly is multi-dimensional.2 Typically several rounds of optimization must be performed to eventually obtain a clinical candidate.
Before describing particular optimization strategies in more detail, we shall define what we mean by an "optimization problem" (Definition 1.1) (adapted from Papadimitriou and Steiglitz).3
Additional chapters from this book:
Analysis of Chemical Space
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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 ...
Evolutionary De Novo Design
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"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
Gisbert Schneider
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...
