A return to rational drug discovery: computer-based models of cells, organs and systems in drug target identification

Abstract

Identifying drug targets successfully requires that we understand the functional interactions between the key components of cells, organs and systems, and how these interactions change in disease states. This information does not reside in the genome, or even in the individual proteins that genes code for. There is therefore no alternative to copying nature and computing these interactions to determine the logic of healthy and diseased states. The rapid growth in biological databases, models of cells, tissues and organs, and in computing power has made it possible to explore functionality all the way from the level of genes to whole organs and systems. Examples are given of identification of multiple target therapy, of counterintuitive drug leads, and of the use of in silico technology in predicting drug safety. This technology is set to transform all stages of drug discovery and development.

• cardiac arrhythmia
• cardiac ischaemia
• computer modelling
• congestive heart failure
• drug safety testing
• ECG modelling
• genome
• in silico cells
• in silico organs
• multiple target therapy
• physiome
• protein interactions
• proteome
• QT prolongation