The pharmaceutical world has been in a state of disarray for quite a while. With most low-hanging fruits already picked, drug discovery seems riskier and more uncertain than ever. Projects often get terminated in mid-stage clinical trials, new targets are getting harder to find, and successful therapeutic agents are often recalled as unanticipated side effects are discovered. What or who is to blame for these problems, all reflecting a lack of resilience to long-term attrition in the discovery pipeline? To answer this complex question we need to come to grips with the fact that drug discovery is anything but rational and tenuously grounded in innovative fundamental research. Mostly based on trial and error and sheer serendipity, the drug discovery endeavor has not been particularly effective at hedging risk. Yet, risk is what investors are most averse to.
Exploiting the huge output of genomic studies to make safer drugs has proven to be much more difficult than anticipated. More than ever, the lead in the pharmaceutical industry depends on the ability to harness innovative research, and this type of innovation can only come from one source: fundamental research. To withstand the long-term attrition in the discovery pipeline, from the bench to the clinical trial, it is essential to have a rational (some would say structure-based) control of drug selectivity. With its focus on the physico-chemical basis of target specificity, Ariel Fernandez’s book “Transformative Concepts for Drug Design: Target Wrapping” advocates precisely this view. Furthermore, it squarely addresses the problem of long-term attrition by introducing fundamental discoveries in molecular biophysics that hold potential to broaden the technological base of the pharmaceutical industry.
This book takes a fresh and fundamental look at the problem of how to design an effective drug with controlled specificity. Since the novel transformative concepts are unfamiliar to most practitioners, the first part of this book explains matters very carefully starting from a fairly elementary physico-chemical level. The second part of the book is devoted to practical applications, aiming at nothing less than a paradigm shift in drug design. This book is addressed to scientists working at the cutting edge of research in the pharmaceutical industry, but the material is at the same time accessible to senior undergraduates or graduate students interested in drug discovery and molecular design.
The book does not portend to close the discussion or solve the long-standing problem of controlling specificity. Rather, it entices the reader to explore new fundamental territory in his/her quest to address these daunting challenges. The book also leaves aside vast areas of molecular design such as the exploration of chemical space and the discovery of new scaffolds. The author promises to deliver a new book where these aspects will be tightly woven into the physical framework already presented.
Ariel Fernandez's Rocky Biophysics 
I read excerpts of AF’s Transformative concepts… It truly is transformative stuff! I always knew there was something missing in rational drug design, and maybe it is right there in AF’s book. The book is NOT for beginners as the Amazon reviewers claim! You better learn your biophysics of proteins before you even lay hands on this book. But I think it is rewarding as it tells you how to target the interface, rather than the protein structure.
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