“Biomolecular Interfaces: Interactions, Functions and Drug Design”, the Latest Book by Ariel Fernandez

A new book by Ariel Fernandez has made its appearance on April 21, 2015. It is entitled “Biomolecular Interfaces: Interactions, Functions and Drug Design“. The publication particulars are:


The book consists of fifteen chapters and covers vast intellectual territory, from statistical thermodynamics to molecular medicine. Its foreword has been written by Prof. Richard L. Moss, the eminent cardiologist from Wisconsin who is a coninventor with Ariel Fernandez in a recent patent to treat heart failure. All in all, the book may place Ariel Fernandez at the center of a veritable biotechnological transformation.

Foreword by Richard L. Moss

The book deals with a largely overlooked area of molecular biophysics that is likely to have strong impact on molecularly targeted medicine and drug design:the aqueous interface of a soluble protein.  Foundational knowledge is presented in the first 7 chapters and enables the reader to effectively tackle major problems in biophysics, such as the protein folding problem and the therapeutic disruption of protein-protein associations.  These advances have been heralded by others, as is evident, for example, in this review published in Scientific American.

The remaining 8 chapters deal with medical applications mostly centered on rational drug design guided by the interfacial patterns of the protein targets.  Some of these advances involve reworking anticancer drugs to make them safer and less toxic and to control their specificity, all of which are reviewed in great detail.  This novel type of design was enthusiastically received by eminent physician scientists such as Thomas Force (Vanderbilt University) and was also covered in very promising terms for example in this review by Harvard oncologist George Demetri.  Quoting Dr. Demetri: “The first generation of kinase-inhibitory drugs such as imatinib and sunitinib have already provided patients with life-saving therapeutic options, and with tools such as those described by Fernández et al., the future certainly looks bright for constructing ever-better agents that can be combined safely and effectively to manage, and eventually cure, many forms of human cancer”.  These seminal advances are further enriched in the book with a description of novel molecular design concepts that enable us to therapeutically disrupt protein-protein interfaces.  This problem is considered to be a holy grail of molecular targeted therapy.  Therapeutic opportunities stem from the advances described in the book.  One illustration is provided in the potential treatment of heart failure by disrupting a myosin association with a myosin-regulatory protein, an invention with a pending patent by this reviewer (Richard Moss) and the author of the book.

All in all, the book reports considerable conceptual novelty rooted in fundamental knowledge that needs to find its way into the pharmaceutical discovery and development pipeline, in particular in the hit-to-lead and lead optimization phases.  Paraphrasing George Demetri, we conclude that the approach by Fernández and coworkers holds great promise for customized development of rationally designed therapeutic agents.

Richard L. Moss, Ph.D., Rennebohm Professor of Cell and Regenerative Biology, Dean, University of Wisconsin School of Medicine and Public Health


The decades that followed the successful forays in structural biology have
witnessed a veritable deluge of research publications in the next frontier discipline:
molecular biophysics. Despite much effort, the core problems in the field remain
stubbornly open and the field has not enjoyed, at least so far, the meteoric level of
success of structural biology. The stakes are high, the science is loud, and yet, the
signal-to-noise ratio in the conveyance of information remains deceptively low. In
spite of enticing promises, it is felt that we are nowhere near cracking the protein
folding problem from first principles, that we are far from unraveling the physical
basis of enzyme catalysis and protein associations, and that we are still
unable to engineer therapeutic drugs based on our understanding of molecular
interactions. In regards to the latter problem, drug discovery seems riskier than ever,
with projects routinely terminated at mid-stage clinical trials, new targets getting
harder to find, and therapeutic agents recalled due to unanticipated health threats or
idiosyncratic side effects in patient subpopulations. The vast and seemingly endemic
problems of the pharmaceutical industry are not confined to the scientific realm
but the latter has much to do them. Properly harvesting and ultimately exploiting
the output of structural biology to make more efficacious and safer drugs has proven
to be much more difficult than originally thought. This rather grim reality has
motivated the writing of this book as it keeps reminding us that conceptual
breakthroughs in the realm of molecular biophysics are sorely needed.

The book focuses on a vital area of biophysical research that has been—in the
author’s view—substantively overlooked if not relegated, an area from within many
of the needed breakthroughs are likely to sprout: the physics of biomolecular
interfaces. The book advocates its paramount relevance to tackle some of the core
problems in molecular biophysics in a unified systematic manner. To this effect, the
book introduces powerful theoretical and computational resources and is set to
inspire scientists at any level in their careers determined to address the major
challenges in the field.

The acknowledgment of how exquisitely the structure and dynamics of proteins
and their aqueous environment are entangled attests to the overdue recognition that
biomolecular phenomena cannot be effectively understood without dealing with
interfacial behavior. There is an urge to grasp how biologically relevant behavior is
mediated and affected by the structuring of biomolecular interfaces. This book
squarely addresses this need, heralding the advent of a new discipline that the
author has aptly named epistructural biology. This field may be broadly described
as the physicochemical study of the reciprocal influence between water and
biomolecular structure across the interface. Given its scope, the book ends up
covering vast intellectual territory. It has to, because the subject is highly
demanding and requires a multidisciplinary approach.

With the advent of sophisticated techniques for probing and modeling
biomolecular systems, it seems likely that epistructural biology will emerge as a
vigorous area of research, impacting core areas of biophysics, including protein
folding, enzyme catalysis, protein associations, and drug/ligand design.

Since the days of J.W. Gibbs or perhaps earlier, physical chemists have realized
that where different phases meet, unusual things are likely to happen. Even for
interfaces modeled as sharp discontinuities between bulk phases—where, say,
a liquid meets a solid—the mere solution of continuity generates surface-associated
phenomena such as interfacial tension. The free energy cost of spanning the interface
makes the latter a locus for unexpected phenomena. One wonders whether, had the
pioneers of surface physics been confronted with the complexity of biological
interfaces laid bare in the recent decades, they may not have turned to other projects
in despair at their ungainliness.

The closer we look, the greater the complexities of biological interfaces appear
to be. Episteric (“around the solid”) water relinquishes its bulk-like character and
even fails to align with the electrostatic field due to tight geometric confinement
coupled with short-range intermolecular forces. These deviations from bulk properties
can enhance the chemical inhomogeneity of protein surfaces by altering the
dielectric properties of interfaces in unfathomable ways. Furthermore, biological
interfaces may be significantly enriched in ions relative to bulk water, an effect with
profound consequences for core biophysical phenomena. Even the most basic
questions such as whether episteric water is acidic or basic are still subject to

Interfaces have long been recognized as central to the chemical sciences but
there has been no systematic, cogent effort to understand them, let alone deal with
them in a biochemical context. This book squarely addresses this need and shows
that a masterful understanding of epistructural behavior is of the essence to address
the challenges that have proven unyielding to research efforts.

Recognizing that practitioners may not be familiar with biomolecular interfaces,
the book first introduces the subject at a reasonably elementary level, exploring
its relevance for protein interactions, protein folding, and catalytic function
(Chaps. 1–7). The remaining eight chapters are devoted to molecular targeted
medicine and therapeutic drug design based on the molecular understanding gained
in the first seven chapters. The book first explores biomolecular interfaces from a
physicochemical standpoint, drawing basic relationships between interfacial water
and the structure of soluble proteins (Chap. 1). The analysis leads to the concept of
dehydron, a protein structural defect that causes interfacial tension. Chapter 2
further deals with the physicochemical underpinnings of interfacial tension, demonstrating
its paramount relevance to understand protein associations. Chapter 3
deals with the steering role of the aqueous interface and interfacial tension in the
protein folding process, providing the first semiempirical solution to the protein
folding problem. Chapter 4 draws relations between interfacial tension and protein
hydration patterns that serve as blueprints for epistructure-based drug design.
Chapter 5 examines large concentrations of packing defects (dehydrons) as causative
of misfolding and aberrant aggregation phenomena and explores the connection
between disorder propensity, misfolding, and dehydron concentration. An
exercise in this chapter deserves particular attention as it leads the reader to discovering
a therapeutic disruption of a protein–protein interface based on rational
design, a holy grail in the field. Chapter 6 explores biomolecular interfaces from an
evolutionary perspective and highlights its relevance for the overarching goal of
achieving specificity in drug design. Chapter 7 deals with the chemical functionality
of biomolecular interfaces as enablers and stimulators of enzyme catalysis. This
chapter contains the highest level of novelty, as it presents the striking finding that
dehydrons prepare the aqueous interface for catalysis. Chapter 8 establishes a
selectivity filter for drug design based on the concepts introduced in Chap. 6.
Chapter 9 describes the redesign of a powerful anticancer drug guided by the
selectivity filter established in Chap. 8. Chapter 10 introduces a bioinformatics
analysis of biomolecular interfaces as universal markers for specificity and personalized
medicine achieved through the therapeutic interference with signaling
pathways. It emphasizes the usefulness of targeting biomolecular interfaces for
personalized molecular treatments tailored to cope with somatic or inherited
mutations that create constitutively deregulated functions. Chapter 11 deals with
dynamic aspects of drug design and drug-induced folding of the protein target,
focusing on dehydron induction. The dynamic concepts and their importance for
molecular engineering are illustrated by the redesign of imatinib into a JNK
inhibitor to treat ovarian cancer. Chapter 12 deals with drug combinations purposely
synergized to edit out side effects and constructed based on the dehydron
selectivity filters described in Chaps. 8–10. Chapter 13 introduces a systems biology
approach to the engineering of wrapping drugs and, consequently, introduces
the control of multi-target drug activity based on the selectivity filters previously
introduced. Chapter 14 introduces the novel modality of immuno-synergic drugs,
that is, anticancer kinase inhibitors redesigned to avoid compromising the immune
response while retaining anticancer activity. Finally, Chap. 15 deals with advanced
quantum mechanical treatments of biomolecular interfaces that empower the paradigm
of “drugs as dehydron wrappers.” These advanced quantum treatments lead
to significant improvements for drug design with the incorporation of halogens in
the chemical scaffolds.

The book is primarily intended as an advanced textbook that may be adopted at
the senior undergraduate level or graduate level and it also reads as a monograph for
practitioners. Fruitful reading requires a thorough background in physical chemistry
and biochemistry. The selected problems at the end of the chapters and the progression
in conceptual difficulty make it a suitable textbook for a graduate level
course or an elective course for seniors majoring in chemistry, biophysics, biomedical
engineering, or related disciplines. The material would be especially adequate
for courses dealing with the Thermodynamics and Physical Chemistry of
Biomolecular Systems, with Fields, Forces and Flows in Biological Systems, and
with Biological Engineering Design.

Excerpts from the Epilogue

This book covers broad knowledge territory, from statistical mechanics to
molecular medicine, and does so by exploring a vast interdisciplinary frontier:
biomolecular interfaces. By drawing relationships between protein structure and the
aqueous interface beyond, the book introduces a new subject aptly named
epistructural biology. The efficacy of this discipline to tackle core problems in
biophysics is demonstrably argued in Chaps. 1–7 and its pivotal role in the “hit-tolead”
and “lead optimization” phases of drug development is highlighted in the
remaining eight chapters of the book. Yet, as is often the case in science, a creative
solution to standing problems introduces new challenges as it shifts the research
frontier. Thus, epistructural biology redefines the established concept of molecular
recognition in light of the pivotal role of packing defects or dehydrons as recognition
elements, steers of protein folding and enablers of enzymatic catalysis. These
fundamental discoveries will surely invite studies leading to establish the role of
dehydrons as key players in redox enzymatic reactions. Of particular interest would
be to delineate the role of dehydrons as steers of redox-state–dependent organization
of water molecules at the interface with the protein structure in order to recruit
and steer proton transfer pathways (cf. Chap. 7). With the knowledge landscape
thus altered, new [meta-]problems [will surely] show up in the research horizon as
one explores what would now be termed the dehydron-mediated biomolecular
recognition of structured water.

Book highlights

Recent Amazon Review

Review Title: Epistructural Biology

By Forbes B. on May 14, 2015
Format: Hardcover

First and foremost, this book addresses an issue that is very important in protein research, namely, the interactions between a protein molecule and its surrounding water environment. This very complicated relationship is often simplified or ignored in molecular modeling. Such an ill-considered strategy simplifies the model but leads to unrealistic predictions of molecular behaviour. By contrast, this book introduces the reader to Epistructural Biology, a model that covers various important aspects of the protein-water interaction. The model is explained with an articulate clear writing style and backed up with enough mathematics to put the ideas on a firm theoretical foundation. The book is suitable for advanced undergraduate and graduate students. To help the student assimilate the ideas, the chapters include several problems with solutions. This is an excellent introduction for students wanting to get a start in Epistructural Biology.



Main Websites:

Scientific website

Ariel Fernandez Consultancy

AF Innovation

Ariel Fernandez ResearchGate

Ariel Fernandez Google Scholar Citations

Ariel Fernandez Wikipedia (Mandarin)

Ariel Fernandez Baidu Encyclopedia (Mandarin)

Ariel Fernandez Books

Current Positions

  • Senior Investigator, Argentine National Research Council (CONICET) (2011-). Argentine Institute of Mathematics (I. A. M.) “Alberto P. Calderón”, 1083 Buenos Aires, Argentina
  • Expert scientifique, Comité d’Evaluation Scientifique, Innovation Biomédicale, Agence Nationale de la Recherche, France (2015-)
  • Honorary Investigator, Collegium Basilea, Institute of Advanced Study, CH 4053 Basel, Switzerland (2006-)
  • Visiting Professor, National Tsing-Hua University, Hsinchu, Republic of China (2010-)
  • President, AF Innovation, SRL, a Pharmaceutical Consultancy (2010-).
  • Vicepresident and Chief Scientific Officer at Ariel Fernandez Consultancy, GmbH, a Biotechnology firm specialized in dynamic molecular design (2013-)

Past Appointments

  • Karl F. Hasselmann Chaired Professor of Engineering, Rice University, Department of Bioengineering, Rice University, Houston, TX 77005 (2005-2011)
  • Professor of Bioengineering, Rice University, 2005-2011 (retired)
  • Rice Research Professor (2011)
  • Adjunct Professor of Molecular Therapy, M. D. Anderson Cancer Center (UTMC) (2006-)
  • Adjunct Professor (2006-2008) and Visiting Scholar (2008-2012), Computer Science Department, The University of Chicago.
  • Senior Scientific Consultant, Eli Lilly and Company (2004- ).


  • Sr. Research Scientist, Max-Planck-Institut fuer biophysikalische Chemie, Division of Nobel Laureate Manfred Eigen, Goettingen, Germany, 1986-1989.
  • Research Associate (1985-1987), Visiting Senior Research Scientist (1994-1996), Princeton University.
  • Licenciado en Matematica (1980), Quimico (1979), Universidad Nacional del Sur, Bahia Blanca, Argentina.


  • Intelligence   IQ 151 (test# e2a3fa0b)
  • Citations*      3369
  • h-index*        30
  • i10-index*      94

(*) Source: Google Scholar Citations for Ariel Fernandez

Summary of Accomplishments

Ariel Fernández introduced what appears to be the correct formulation for self-organization in nonequilibrium thermodynamics by realizing that the thermodynamically relevant degrees of freedom must belong to a center manifold, an algebraically closed entity, and not to an attractor, as Ilya Prigogine previously assumed. He has provided a semiempirical solution to the protein folding problem by introducing the episteric tension, a measure of the distortion of the water structural matrix that requires a multi-scale theory of dielectrics. He rationally discovered a ligand that would competitively disrupt a protein-protein interface for therapeutic purposes (patent pending). He also managed to predict and control induced folding in drug-target associations. Together with Ridgway Scott, he introduced the dehydron, a structural defect in proteins that promotes its own dehydration. A dehydron is a meta-structural feature of relevance in drug design, enzyme catalysis and protein folding. Ariel Fernández determined and measured the dehydronic field, the mechanical equivalent of the dehydration propensity of a dehydron exerted on a test nonpolar molecule and orthogonal to the Coulombic field. His current efforts are devoted to show that dehydrons are endowed with a catalytic role as enablers and stimulators of enzymatic activity.

Awards and Previous Appointments

  • Camille and Henry Dreyfus Teacher-Scholar Awardee, 1991
  • Camille and Henry Dreyfus Distinguished New Faculty Awardee, 1989
  • John S. Guggenheim Memorial Foundation Fellow, 1995-1996
  • Consultant to U.S. Federal Government, NIH, Special Panel on Centers of Excellence in  Systems Biology, 2003-
  • National Cancer Institute (NCI) Reviewer. NIH Study Section RFA-07-005 “Advanced Proteomic Platforms and Computational Sciences for NCI Clinical Proteomic Technologies Initiative”, 2006-
  • Guest Professor, Institute for Protein Research, Osaka University, Japan, 2003
  • Visiting Senior Researcher, Max-Planck-Institut fuer Biochemie, Abteilung Robert Huber, Martinsried, Germany, 2000-
  • Visiting Senior Scientist, Institute for Nonlinear Science, University of California at San Diego, 1989
  • Managing Editor, Frontiers in Bioscience, Encyclopedia of Bioscience, 2006-
  • Editor, Journal of Biological Physics and Chemistry, Basel, Switzerland, 2000-
  • Fulbright Scholar, US Information Agency, 1999 and Fulbright Fellow, 1981
  • Alexander von Humboldt Foundation Awardee (1995)
  • Max Planck Society Scholar, Goettingen, Germany (1987-1989)
  • Feinberg Fellow, Israel, 1984-1985
  • Full Professor, Indiana University School of Informatics, 2003-2005.
  • Full Professor, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, 2003-2005.
  • Elected Fellow, American Institute for Medical and Biological Engineering, 2006
  • Full Professor and Principal Investigator, UNS and Natl. Res. Council of Argentina, 1994-2003.
  • Medal “State of Buenos Aires” to the best graduate, Argentina, 1980
  • Deputy Governor, American Biographical Institute, 1998-
  • Co-organizer and Proceedings Editor of the Miami Bio/Technology Winter Symposium, Nature-sponsored, 1993.
  • Chair, “Resistance and Safety”/Kinase Inhibitors, Cambridge Healthtech Institute’s Sixth Annual “Discovery on Target” Symposium; October 20-23, Boston, MA, USA, 2008.
  • Honorary Member, Collegium Basilea, Institute for Advanced Study, Basel, Switzerland, 2006-
  • Adjunct Professor of Computer Science, The University of Chicago (2005-2008).
  • Editorial Board Member, Journal of Postgenomics: Drug & Biomarker Development – Open Access, OMICS Publishing Group, 2010-
  • Editorial Board Member, Journal of Bioengineering & Biomedical Science, OMICS Publishing Group, 2010-
  • Editorial Board Member, Journal of Metabolomics: Open access, OMICS Publishing Group, 2012-
  • Distinguished Scientific Leader Lecturer, Georgia Institute of Technology, 11/10/2010, Lecture title: “Evolutionary insights into the control of drug specificity”. URL: https://smartech.gatech.edu/handle/1853/36240?show=full
  • Columnist at Project Syndicate, The World’s Opinion Page (2011-)
  • Editorial Board Member, Journal of Pharmacogenomics & Pharmacoproteomics, OMICS Publishing Group, 2015-
  • Expert scientifique, Comité d’Evaluation Scientifique, Innovation Biomédicale (CE18), Agence Nationale de la Recherche, France, 2015-

Legal Consultancies – Pharmaceutical Patent Litigation

  • Schiff/Hardin, LLP (Chicago-based Law Firm).
  • Racoczy, Molino, Mazzocchi and Siwik, LLP (Chicago-based Law Firm)

Recent Grant support, PI: Ariel Fernandez

  • NIH Grant Award 1R01 GM072614 from the National Institute of General Medical Sciences (NIGMS). Title: “Protein packing defects as functional markers and drug targets”. Total amount of award: $1.6million (2005-2009).
  • Eli Lilly and Company, Unrestricted research funds (2004-)


  • US 8,466,154 B2 (granted)

Ariel Fernández et al.: “Methods and Composition of Matter Related to Wrapping of Dehydrons”. Inventors: Ariel Fernández, William Bornmann, Gabriel Lopez-Berestein, Angela Sanguino, Zeng-Hong Peng, Anil K. Sood. Awarded: June 18, 2013.

  • US 20130345135A1 (pending)

Richard L. Moss and Ariel Fernández: “Inhibition of MYBP-C binding to myosin as a treatment for heart failure”. Inventors: Richard L. Moss and Ariel Fernández; Asignee: Wisconsin Alumni Research Foundation.


  • Author: Ariel Fernández

Title: “Transformative Concepts for Drug Design: Target Wrapping

Publisher: Springer, Heidelberg, Berlin (240 pages)

ISBN: 978-3-642-11791-6

Publication year: 2010.


  • Author: Ariel Fernández Stigliano

Title: “Biomolecular Interfaces: Interactions, Functions and Drug Design

Publisher: Springer, Heidelberg, Berlin (372 pages)

ISBN: 978-3319168494

Publication year: 2015.


Selected Recent Publications

Sources: ResearchGate, Google Scholar Citations, Baidu Encyclopedia (Mandarin) and Wikipedia (Mandarin)

  1. Ariel Fernández and Harold A. Scheraga: “Insufficiently dehydrated hydrogen bonds as determinants for protein interactions”, Proceedings of the National Academy of Sciences, USA 100, 113-118 (2003).
  1. Ariel Fernández and R. Stephen Berry: “Proteins with hydrogen-bond packing defects are highly interactive with lipid bilayers: Implications for amyloidogenesis”, Proceedings of the National Academy of Sciences, USA 100, 2391-2396 (2003).
  1. Ariel Fernández and Ridgway Scott: “Adherence of packing defects in soluble proteins”, Physical Review Letters 91, 018102, 4 pages (2003).
  1. Ariel Fernández, Jozsef Kardos, Ridgway Scott, Yuji Goto and R. Stephen Berry: “Structural defects and the diagnosis of amyloidogenic propensity”, Proceedings of the National Academy of Sciences, USA 100, 6446-6451 (2003).
  1. Ariel Fernández, L. Ridgway Scott and R. Stephen Berry: “The nonconserved wrapping of conserved folds reveals a trend towards increasing connectivity in proteomic networks”. Proceedings of the National Academy of Sciences, USA 101, 2823-2827 (2004).
  1. Ariel Fernández, Kristina Rogale, L. Ridgway Scott and Harold A. Scheraga: “Inhibitor design by wrapping packing defects in HIV-1 proteins”. Proceedings of the National Academy of Sciences, USA 101, 11640-11645 (2004).
  1. Ariel Fernández and R. Stephen Berry: “Molecular dimension explored in evolution to promote proteomic complexity”. Proceedings of the National Academy of Sciences, USA 101, 13460-13465 (2004).
  1. Ariel Fernández: “Keeping Dry and Crossing Membranes”. Nature Biotechnology 22, 1081-1084 (2004).
  1. Florin Despa, Ariel Fernández and R. Stephen Berry: “Dielectric modulation of biological water”. Physical Review Letters 93, 228104 (4 pages) (2004). Featured in Nature (News and Views) 432, 688 (2004).
  1. Ariel Fernández: “Incomplete protein packing as a selectivity filter in drug design”. Structure 13, 1829-1836 (2005).
  1. Jianping Chen, Xi Zhang and Ariel Fernández: “Molecular basis for specificity in the druggable kinome: sequence-based analysis”. Bioinformatics 23, 563-572 (2007).
  1. Ariel Fernández et al.: “Rational Drug Redesign to overcome drug resistance in cancer therapy: Imatinib moving target”. Cancer Research 67, 4028-4033, Priority Report, Cover featured (2007).
  1. Ariel Fernández, et al.: “An anticancer C-kit kinase inhibitor is re-engineered to make it more active and less cardiotoxic”. Journal of Clinical Investigation 117, 4044-4054 (2007). (featured in Press Releases). Commentary by George Demetri: Structural reengineering of imatinib to decrease cardiac risk in cancer therapy. Journal of Clinical Investigation 117, 3650-3653 (2007).
  1. Ariel Fernández: “Molecular basis for evolving self-dissimilarity in the yeast protein interaction network”. PLoS Computational Biology 3, e226 (2007).
  1. Ariel Fernández, Xi Zhang and Jianping Chen: “Folding and wrapping soluble proteins: Exploring the molecular basis of cooperativity and aggregation”. Progress in Molecular Biology and Translational Science 83, 53-88 (2008).
  1. Xi Zhang, Alejandro Crespo and Ariel Fernández: “Turning promiscuous kinase inhibitors into safer drugs”. Trends in Biotechnology 26, 295-301 (2008).
  1. Ariel Fernández and Alejandro Crespo: “Protein wrapping: a marker for association, aggregation and molecular targeted therapy”. Chemical Society Reviews (Royal Society of Chemistry, UK) 37, 2373-2382, Tutorial Review (2008).
  1. Jianping Chen, Han Liang and Ariel Fernández: “Protein structure protection commits gene expression patterns”. Genome Biology 9, R107 (2008).
  1. Ariel Fernández, Soledad Bazán and Jianping Chen: “Taming the induced folding of drug-targeted kinases”. Trends in Pharmacological Sciences 30, 66-71 (2009)
  1. Ariel Fernández and Jianping Chen: “Human capacitance to dosage imbalance: Coping with inefficient selection”. Genome Research 19, 2185-2192 (2009).
  1. Ariel Fernández and R. Stephen Berry: “Golden rule for buttressing vulnerable soluble proteins”. Journal of Proteome Research (ACS) 9, 2643-2648 (2010).
  1. Larisa Cybulski, Mariana Martin, Maria Mansilla, Ariel Fernández and Diego de Mendoza: “Membrane Thickness Cue for Cold Sensing in a Bacterium”. Current Biology 20, 1539-1544 (2010). Editorially commissioned review by Kumaran Ramamurthi, Current Biology 20, R707-R709 (2010). Research Highlight in Nature Reviews/Microbiology: Lucie Wootton: “Bacillus takes the temperature”. Nature Reviews/Microbiology 8, 680 (2010).
  1. Ariel Fernández: “Nanoscale Thermodynamics of Biological Interfacial Tension”, Proceedings of The Royal Society A 467, 559-568 (2010).


  1. Ariel Fernández: “Variational mechanics of water at biological interfaces”. Fast Track Communication. Journal of Physics A: Math. Theor. 44, 292001 (2011).
  1. Ariel Fernández and Michael Lynch: “Nonadaptive origins of interactome complexity”. Nature 474, 502-505 (2011).
  1. Ariel Fernández, Christopher Fraser and L. Ridgway Scott: “Purposely engineered drug-target mismatches for entropy-based drug optimization”. Trends in Biotechnology 30, 1-7 (2012).
  1. Ariel Fernández: “Communication: Epistructural thermodynamics of soluble proteins”. Journal of Chemical Physics 136, 091101 (2012).
  1. Ariel Fernández: “Epistructural tension promotes protein associations”. Physical Review Letters 108, 188102 (2012). Reviewed in Physics (American Physical Society). Focus: “Proteins Hook up Where Water Allows”. Physics 5, 51 (2012). Reviewed in Chemical & Engineering News “Protein Binding Hot Spots”. Chemical & Engineering News 90 (20), 39 (2012)
  1. Ariel Fernández: “Comunication: Nanoscale electrostatic theory of epistructural fields at the protein-water interface”. Journal of Chemical Physics 137, 231101 (2012).
  1. Ariel Fernández Stigliano: “Breakdown of the Debye polarization ansatz at protein-water interfaces”. Journal of Chemical Physics 138, 225103 (2013).
  1. Ariel Fernández: “Supramolecular evolution of protein organization”. Annual Reviews of Genetics, in press (2015).
  1. Ariel Fernández: “The principle of minimal episteric distortion of the water matrix and its steering role in protein folding”. Journal of Chemical Physics 139, 085101 (2013).
  1. María Eugenia Inda, Michel Vandenbranden, Ariel Fernández, et al.: “A lipid-mediated conformational switch modulates the thermosensing activity in DesK”. Proceedings of the National Academy of Sciences USA 111, 3579-3584 (2014). Reviewed in Research Highlights – Nature Chemical Biology 10, 240 (2014)
  1. Ariel Fernández: “Synergizing immunotherapy with molecularly targeted anticancer treatment”. Drug Discovery Today 19, 1427-1432 (2014).  http://www.sciencedirect.com/science/article/pii/S135964461400107X
  1. Ariel Fernández: “Water promotes the sealing of nanoscale packing defects in folding proteins”. Journal of Physics: Condensed Matter – Fast Track Communications 26, 202101 (2014).
  1. Ariel Fernández: “How do proteins dry in water?” Journal of Physics: Condensed Matter – News Item, May 1 (2014). Published at: http://iopscience.iop.org/0953-8984/labtalk-article/57046
  1. Ariel Fernández: “Communication: Chemical functionality of interfacial water enveloping nanoscale structural defects in proteins”. Journal of Chemical Physics 140, 221102 (2014).
  1. Ariel Fernández: “Packing defects functionalize soluble proteins” FEBS Letters 589, 967-973 (2015). Featured in Journal Cover.
  1. BOOK I

Author: Ariel Fernández

Title: “Transformative Concepts for Drug Design: Target Wrapping

Publisher: Springer, Heidelberg, Berlin (240 pages)

ISBN: 978-3-642-11791-6

Publication year: 2010.

  1. BOOK II

Author: Ariel Fernández Stigliano

Title: “Biomolecular Interfaces: Interactions, Functions and Drug Design

Publisher: Springer, Heidelberg, Berlin (372 pages)

ISBN: 978-3319168494

Publication year: 2015.

Book Foreword and Highlights


349. US 8,466,154 B2 (awarded)

Ariel Fernández et al.: “Methods and Composition of Matter Related to Wrapping of Dehydrons”. Inventors: Ariel Fernández, William Bornmann, Gabriel Lopez-Berestein, Angela Sanguino, Zeng-Hong Peng, Anil K. Sood. Awarded: June 18, 2013.

350. US 20130345135A1 (pending)

Richard L. Moss and Ariel Fernández: “Inhibition of MYBP-C binding to myosin as a treatment for heart failure”. Inventors: Richard L. Moss and Ariel Fernández; Asignee: Wisconsin Alumni Research Foundation.


  1. Ariel Fernández: “Human Evolution: No Easy Fix”. Project Syndicate (The World’s Opinion Page), Culture and Society Section, October 3, 2011. Published at: http://www.project-syndicate.org/commentary/human-evolution–no-easy-fix
  1. Ariel Fernández: “Structural Defects in Proteins May Function as Catalysts, Study Reveals”, Press Release: Discovery of the Catalytic Dehydron, WebWire, July 6, 2014.
  1. Ariel Fernández: “Protein Structural Defects Are Enablers and Stimulators of Enzyme Catalysis”. PR Newswire, July 14, 2014.

Reproduced in:  Yahoo News, The Wall Street Journal  – MarketWatch.


Related Reading

Ariel Fernandez complete CV (Updated 5/12/2015)

Book Flyer

Ariel Fernandez Biotechnology Consultancy

Ariel Fernandez Wikipedia (Mandarin)

Ariel Fernandez Wikipedia (English)

Ariel Fernandez Wikipedia (Spanish)



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