Current Computer-Aided Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811
USA

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Post-Genomic Design of Bioactive Molecules

Author(s): Martin G. Grigorov.

Abstract:

This article is presenting the most recent trends in the ways that the bioactive molecules of the future will be designed. They rely on important recent discoveries for our understanding of the global organization of the cell, giving evidence that biological networks form small-world and scale-free structures. These networks are composed of well-defined modules, with nodes connected by relatively short paths that allow for fast signaling. The few very connected nodes, that are unlikely to be affected by random alterations, support the proper functioning of the whole system. The fact that in cells everything is connected to everything explains why monogenic diseases, associated to the alteration of individual genes, were found to be an exception rather than a rule. The newly developed chemogenomic technology is offering an alternative to the traditional animal-centric pharmacological approach in the need to evaluate bioactive molecules efficacy on intact biological systems, where the multiple targets and pathways reside in their natural environment. The existence of regulatory and interaction neural centres or hubs in these networks is setting new perspectives to target identification and validation. With these new technologies at hand, we are entering an exciting new era where the pharmacological targets will shift from single proteins, to functional protein complexes, to whole networks determining precise cellular states, and where the new cures and foods will be no more based on single active ingredients but will represent molecular cocktails or multiple ligands with components targeting the neural centers of whole disease-associated molecular networks.

Keywords: chemogenomics, scale-free networks, small-world networks, design of bioactive molecules, cheminformatics, structure-based molecular docking, in silico screening, bitter taste receptors

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Article Details

VOLUME: 1
ISSUE: 2
Year: 2005
Page: [147 - 162]
Pages: 16
DOI: 10.2174/1573409053585690
Price: $58