Biosystems modelling for in silico target validation: challenges to implementation

Abstract

Computer simulation of biological systems for in silico target validation has the potential for increasing the efficiency of pharmaceutical R&D by expanding the number of parameters tested ‘virtually’. Only the most interesting subset of these has to then be probed in vivo. By avoiding less informative experiments and focusing on variables with the greatest influence on clinical end points, valuable drug targets can be advanced more quickly and those with little or no leverage bypassed. With many compounds failing today due to insufficient efficacy, use of in silico methods should lead to a greater percentage of compounds making the transition to clinical drug. Though biosystems modelling has great advantages, the actual adoption and implementation within each organisation will be a variable process because it has a disruptive approach to current pharma R&D practices. Some companies may have scientific personnel, technical infrastructure and a management culture that provide fertile ground for such a change; other companies will likely struggle more than once to adopt such methods. Innovators need to understand the challenges to implementation they will face and what actions are likely to improve their chances of success. Organisations which successfully implement biosystems modelling for in silico target validation should be able to design experiments and trials more tailored to each drug target and thus achieve higher yields of approved drugs from compounds tested.

• biological systems modelling
• cellular automata
• computer simulation
• diffusion of innovation
• disease modelling
• implementation
• in silico target validation
• top-down modelling