Pathway Analysis for Drug Discovery

This book is a compilation of articles by pioneers of pathway analysis. While providing some solutions and the state – of – the – art overview, the book formulates many questions that yet to be addressed by the scientific community. The phrase “drug discovery” in the title was intended to emphasize the pragmatic approach for the book.

Pathway analysis attempts on the enormous task of formalizing the molecular biological knowledge to make it suitable for predictive computation. Pathway analysis is currently in its infancy and requires the framework for thinking and development of useful applications. This framework can only be based on practical solutions that have a direct impact on human life and well – being of society. Improving human health and optimizing biological organisms for human needs are two main practical applications of molecular biology that rapidly move it away from being an academic discipline toward the application science in commercial industry.

Drug discovery industry is likely to benefit most from pathway analysis. There are two major computational challenges in the drug development. First is calculating the structure of drug molecules that have specific and predictable protein targets and therefore predictable biological effects. Second is calculating the biological effects themselves. Both tasks require extensive computational resources but use very different fundamental principles. The structural drug design is based on physics of molecular structure and interaction while calculating biological effects is based on the analysis of information flow or pathways. Even though the information flows inside the living cell through the physical interaction network, the physics of the molecular interactions has limited effect on biological pathways. Instead, the combinatorial effect from players in the protein community network determines the biological outcome of the drug treatment, disease progression, and healthy signaling throughout the human body. The computational complexity in structural drug design is due to the large number of atoms participating in the molecular interaction, while the complexity of pathway analysis is due to the large number of processes that occur in a single human cell, multiplied by the large number of tissues in human organism.

Currently used approach of “computing” the drug effects using live organisms such as animal models and patients in clinical trials is expensive, error prone, and can be viewed as unethical. Therefore, everyone appears to believe that in silico predictions should be the safest and most economical way of improving the drug discovery pipeline. Because the excuse of having insufficient computational resources rapidly vanishes into the history, the book attempts to summarize critical elements that are necessary for successful in silico pathway analysis for drug development.